Poster Session

POSTER SESSION

PS1-THU-006

Behavior disorders and quality of life in children and adolescents with renal transplantation

A. Madrid* ¹, S. Chocron¹, E. Lara¹, R. Vilalta¹, M. Muñoz¹, C. Herrero¹, J. Nieto¹

¹Pediatric Nephrology and Transplant Department, Hospital Vall d’Hebron, Barcelona, Spain

Medical advances have helped the majority of pediatric renal transplant patients to survive into adulthood, so the optimal care of these patients includes adequate Psychosocial development to achieve a successful transition to adulthood. An observational and descriptive study, and to determine the prevalence of behavioral disorders and quality of life in 41 renal transplant children and adolescents aged between 5 and 18. The measurement instrument was the survey.

Nursing evaluation: Good motivation on the part of the patient to follow the treatment, but the patient also feels exhausted by the chronic nature of it.

Nutritional: Percentage of patients with obesity and excess weight superior to that of the healthy population, with major predominance in the early post transplant (<6 months) and those that were receiving steroids. This associated with other factors as dyslipidemias, arterial hypertension and scarce physical activity increase the cardiovascular risk, therefore the evaluation and education pre and post transplant will help to prepare the co-morbid states.

Educational: A negative effect was stated in most areas of learning and school aspects, interfering with the acquisition of basic knowledge, more so the longer and more severe the base illness was pre transplant.

Socio-familiar evaluation: Illness situation increased the chance of labor loss of one of the progenitors in some cases. The principal needs perceived by the familial group were the need for major socio-familiar support, economic support, orientation and advice.

Behavioral and emotional disorders: High predominance of psychiatric disorders arose with co-morbidity, which highlights the need for paido-psichiatric evaluation pre and post transplant. The quality of life was significantly below average compared to the healthy population. Although with the age it improves in the patient, the evaluation on the part of the parents remains very negative.

PS1-THU-007

BK virus in pediatric kidney transplanted patients: incidence, diagnosis, therapy and outcome

A. Madrid* ¹, S. Chocron¹, E. Lara¹, R. Vilalta¹, M. Muñoz¹, C. Herrero¹

¹Pediatric Nephrology and Transplant Department, Hospital Vall d’Hebron, Barcelona, Spain

In our center 58 pediatrics patients received a kidney graft from 2006.5 patients (8.6%) had presented BK viremia positive. All patients transplanted were tested for BK Polyomavirus by PCR.

We found two patients with viremia positive without BKVAN. The appearance was between 3er month and 12th month. Another 3 patients presented BKVAN consequent upon their positive viremia appearing between 11th and 122 month. These 3 patients had been submitted to severe immunity suppression. The induction treatment in the current transplant has been with thymoglobulin/Steroids followed by standard immunosuppression. The BKVAN in these patients appeared for polyuria, proteinuria and decrease of glomerular filtration . The renal biopsy showed BKVAN grade B in two patients and C in the patient 1.

The both patients without nephropathy the treatment was reduction in immunosuppression: withdrawn MMF and reduced tacrolimus 50% of dose . Both patients had a good evolution with disappearance of BK in blood in 6 months. The 3 patients with BK nephropathy underwent the same immunosuppression and also plan have been treated with cidofovir, withdram of mycophenolate, FK reduction with levels of 4 ng/ml, in two of them and the third change low-dose everolimus.

The evolution of patients with nephropathy degree C evolved with the loss of the graft, both patients with grade B have evolved correctly with the negative viremia and normalization of renal function. The type B nephropathy may be reversible, while type C is irreversible. BKVAN is cause of irreversible graft failure.

We found that with reduction of immunosuppression, it’s not enough for reduce the viral loads, and don’t go to progression to BKVAN. The Cidofovir indication is clearly established when we have a BKVAN.

PS1-THU-008

Acylcarnitine profile in end-stage renal disease (ESRD) patients

E. Sulyok* ¹, B. Csiky^2,3, J. Bene⁴, I. Wittmann³, B. Melegh⁴

¹Institute of Public Health and Health Promotion Faculty of Health Sciences, University of Pécs, Pécs, Hungary FMC Dialysis Center, Pécs, Hungary, ²2nd Department of Internal Medicine Faculty of Medicine, University of Pécs, Pécs, Hungary, ³Department of Medical Genetics and Child Development, Faculty of Medicine, University of Pécs, Pécs, Hungary

Objective: Patients with ESRD on regular hemodialysis (HD) frequently encounter carnitine depletion and accumulation of acylcarnitines (ACs). This study was carried out to investigate -the effects of l-carnitine supplementation on AC profile, -the dynamic response of distinct ACs during the single HD session in carnitine repleted state, and -the recovery pattern of ACs during the wash-out period.

Methods: 20 consecutive, non-diabetic adult patients with ESRD on HD for >6 months were selected for this longitudinal study. They received three HD sessions weekly and 1g iv l-carnitine after each session for 12 weeks. Samples were taken for free and ACs before, at the end of supplementation, and at hourly intervals during the first HD session followed by post-HD samplings for 5 weeks. Healthy controls comprised 40 adult patients admitted for elective surgery. Free and AC plasma levels were determined by using ES-MS/MS.

Results: Unsupplemented patients had reduced free- and total carnitine accompanied with elevated ACs and acyl to free carnitine ratio. Short-, medium-chain and dicarboxylic ACs increased invariably, whereas only C14 ACs increased in the long-chain fraction. L-carnitine supplementation resulted in significant elevation to supraphysiological levels of all carnitie compounds. HD induced progressive decline in free, short-chain and dicarboxylic ACs (∼80%), that of medium-chain ACs proved to be more moderate (∼60%) and long-chain ACs remained unaffected. During the wash-out period there was a transient rise in all fractions except for long-chain ACs by 44 hours post-HD followed by a new steady-state at intermediate levels between depleted and replenished values.

Conclusion: Our study established the plasma profile of accumulated ACs in HD patients and described the response of individual ACs to l-carnitine supplementation and HD to understand the complex metabolic abnormalities in uremia.

PS1-THU-012

Should all the children with chronic kidney disease stage 5 in Poland be obligatorily treated with dialysis—attitudes of nephrologists, neonatologists and intensivists?

M. Tkaczyk* ¹, A. Jander¹, J. Stempień²

¹Nephrology Division, Polish Mother’s Memorial Hospital Research Institute, Lodz, Poland, ²Chair of Social Sciences, University of Lodz, Lodz, Poland

Withholding or withdrawing renal replacement therapy consist one of most cumbersome and difficult decision for nephrologists. There are no current guidelines in Poland concerning this issue. Thus, physicians make their decisions based on personal experience and literature data. The aim of this multicentre nationwide study (conducted under auspices of Polish Society for Paediatric Nephrology in 12 paediatric nephrology/dialysis units) was to reveal the attitude of Polish physicians dealing with qualification to chronic dialysis (nephrologists, neonatologists and intensivists) to chronic dialysis withholding or withdrawal in children. The study was addressed to whole population of nephrologists, intensivists and neonatologists dealing with chronic renal replacement therapy for children from key paediatric nephrology centres in Poland. The response rate was 56%. The study revealed that despite the specialty most of respondents accept chronic dialysis withholding or withdrawal as the alternative in selected clinical situations. Physicians reported that comorbidities, long-term prognosis and parents’ opinion had have highest impact on their opinion. The decision process should be conducted by a multidisciplinary team made up of treating physician, head of the department and consulting nephrologists. Most of respondents suggested implementing national guidelines concerning qualification, withholding or withdrawal of chronic dialysis therapy in children. Physicians of longer professional experience and higher professional position (managing) significantly more often opted for this solution.

PS1-THU-017

Can urinary IL8 and 18 serve as early markers of acute kidney injury (AKI) in paediatric cardiac surgery patients?

M. Miklaszewska* ¹, K. Zachwieja¹, P. Korohoda², T. Mroczek³, A. Moczulska¹, D. Drożdż¹, J. A. Pietrzyk¹

¹Paediatric Nephrology and Dialysis Unit, Jagiellonian University Medical College, Kraków, Poland, ²AGH University of Science and Technology, Chair of Electronics, ³Paediatric Cardiosurgery Unit, Jagiellonian University Medical College, Kraków, Poland

Pediatric cardiosurgical procedures with extracorporeal circulation (EC) are associated with a risk of AKI.Evaluation of clinical usefulness of urinary uIL8 and uIL18 in early diagnosis of AKI within 24 hrs postoperatively in children with congenital heart malformations (CHM) subjected EC was aim of study. It included 47 children.Urine samples were collected before EC and 2,6,12,18,24 hrs after EC. AKI was noted in 19(40.4%) patients(pRIFLE criteria).Mean uIL8 and uIL18 values in all patients were 20.74 and 102.88 pg/ml(controls:10.55; 10.7 pg/ml;p = 0.0066;p = 0.0019). Maximum mean values of uIL8 and uIL18 in AKI children were reached in 18th hour (52.6 and 221.11 pg/ml).Mean concentrations of uIL8 and uIL18 were significantly higher in the AKI group(AKI 22.41 vs. no AKI 19.54; p = 0.0224 and AKI 137.81 vs. no AKI 78.10 pg/ml; p = 0.0022). Differential analysis of ln’s median value of uIL8 and uIL18 revealed statistically significant difference in the 6th hour (p = 0.0114; p = 0.0132). Logistic regression analysis for ln of uIL8 and uIL18 concentrations revealed relationship which had shown, that 2.72-times increase of cytokines’ concentrations may implicate an increase of AKI risk by 24.8% and 43.1%, respectively.AUC ROC for uIL8 and uIL18 in the 6th hour for cut-off value of 4.22 and 44 pg/ml were 71% and 72.3%, respectively.Mean concentration of uIL8 and uIL18 was significantly higher in CHM children with AKI. Urine IL8 and IL18 in patients after EC in the 6th postoperative hour seems to be valuable but not an ideal marker indicating a risk of subsequent AKI.

PS1-THU-033

Experience with pediatric automated peritoneal dialysis in R. Macedonia

E. Sahpazova* ¹, D. Kuzmanovska¹

¹University Childrens Hospital, Skopje, Macedonia

Objective: Automated peritoneal dialysis (APD) is considered the first-choice chronic peritoneal dialysis modality for pediatric patients. In this study we describe our experience with pediatric patients on APD.

Methods: 13 years retrospective study of 9 children (3 girls and 6 boys, mean age 7.14 ± 6.69 years) who underwent APD treatment. The mean duration of APD was 43.89 ± 25.84 months (range 14–82 months).

Results: The primary diagnosis was glomerulonephropathies (33.34%), uropathy (55.55%) and hypoplasticidysplastic kidney (11.11%). Peritoneal equilibration test showed that 4 patients (44.45%) were high transporter, 2 patients (22.22%) were high average transporter and 3 patients (33.33%) were low average transporter. The incidence of peritonitis rate was 1 infection in 15.2 patients/months and for exit site infection 1 episode in 44 patients/months. Staphilococcus aureus was the most prevalent pathogens and accounted for 42.3% of the peritonitis, and 44.44% of the ESI. The mean combined weekly creatinin clearance was 4.92 ± 2.87 ml/min/1.73 m² and mean weekly Kt/V urea was 3.53 ± 0.56. During follow-up period 1 patient (11.11%) received renal transplant from living donor. Persisting peritonitis and loss of ultrafiltration in 3 patients (33.34%) was the main cause for transferred to HD and 5 children (55.55%) remained on APD.

Conclusion: APD is a good dialysis modality for pediatric end stage renal failure patients, witch allows for more free time for patients and families. There while achieving adequate dialysis in the majority of patients. Prevention and appropriate therapy of infection complications could prolong patients and technique survival. Our center continues to recommend APD for pediatric patients requiring chronic dialysis.

PS1-THU-034

Three-year data after pediatric KTX: de novo therapy with Everolimus, low-dose ciclosporine a and steroid elimination

L. Pape* ¹, C. Blume², F. Lehner³, T. Ahlenstiel¹

¹Department of Pediatric Nephrology, Medical School of Hannover, Germany, ²Department of Nephrology and Hypertension, Medical School of Hannover, Germany, ³Department of Transplant and Visceral Surgery, Medical School of Hannover, Germany

The number of acute rejections after pediatric KTX could not be reduced in the last years. In order to reduce these events, we investigated a new immunosuppressive protocol in a prospective, controlled trial. Hereby we present the results of the 3 year follow-up.

After KTX twenty children (median age 12 years, range 1–17) were initially treated with Basiliximab, CsA (C0 200–250 ng/ml) and Prednisolone. After 2 weeks, CsA dose was reduced to 50% (C0 75–100 ng/ml, after 6 months: 50–75 ng/ml) and Everolimus (1.6 mg/m²/d) was started (C0 3–6 ng/ml). Nine months after KTX, Prednisolone was stopped.

There was no loss of follow up and no graft or patient loss. In case of s-creatinine increase, 14 indication biopsies were performed: 4 acute tubular necrosis, 5 borderline-findings (in one patient associated with transplant glomerulopathy), 3 interstitial fibrosis, 1 recidive of MPGN II and 1 without pathological findings. No biopsy showed acute rejection BANFF ≥ IA. The mean GFR was 71 ± 25 ml/min/1.73 m² 12 months and 62 ± 2 ml/min/1.73 m² 36 months after KTX. In those patients who were still treated by pediatric nephrologists, 3 yr GFR was 70 ± 23 ml/min/1.73 m², whereas in patients transferred to adult care, GFR was 49 ± 13 ml/min/1.73 m² (p < 0.05). No PTLD and no Polyoma-Nephropathy was diagnosed. After 3 years 18/20 patients were still on their original immunosuppressive regimen.

In pediatric KTX de novo immunosuppression with low-dose CsA, Everolimus and steroid withdrawal after 9 months led to promising results according to numbers of acute rejections and graft survival in the first 3 years after KTX. Transition into adult care is still a risk factor for deterioration of graft function.

PS1-THU-039

Polyoma BK-virus (BKV)-specific T cells as a surrogate marker for polyomavirus-associated-nephropathy (PVAN) after pediatric kidney transplantation

T. Ahlenstiel* ¹, M. Sester², L. Pape¹

¹Department of Pediatric Nephrology, Medical School of Hannover, Hannover, Germany, ²Department of Virology, University of the Saarland, Homburg(Saar), Germany

After kidney transplantation (KTx) immunosuppression causes impaired cellular immune defense resulting in increased risk of PVAN. Prognostic markers for the outcome of BKV-infections are missing. BKV-specific (sp) Tcells may serve as a surrogate marker for BKV-associated complications.

After KTx BKV-sp T cells were examined in 11 children (3–17 years) with current or previous detection of BKV-DNA in blood at different times (a total of 45 tests with a maximum of 11 tests per person). After stimulation with BKV-antigens (VP1;largeT) BKV-sp CD4+ and CD8+ Tcells were identified by flow cytometry.

The majority of our study group (9/11) showed -at least temporarily- BKV-sp CD4+ Tcells (up to 4.2 cells/μl),whereas only 4 patients had BKV-sp CD8+ Tcells (up to 2.0 cells/μl). Children with biopsy proven florid PVAN (n = 3) were characterized by persistent detection of BKV-DNA (>3 months) combined with lack or very low levels of BKV-sp CD4+ Tcells (<0.75 cells/μl). In contrast,in case of high levels of BKV-sp CD4+ Tcells (>0.75 cells/μl) five out of six patients did not show persistent BKV-DNA in blood,suggesting that sufficient levels of BKV-sp CD4+ Tcells (>0.75 cells/μl) enable to overcome BKV-infections. After disappearance of BKV-DNA,BKV-sp CD4+ Tcells were not permanently detectable in some patients.

In case of BKV-DNA-detection in blood,low levels of BKV-sp CD4+ Tcells are associated with increased risk of florid PVAN,whereas patients with sufficient BKV-sp CD4+ Tcells do not develop BKV-associated complications. Serving as prognostic marker for individual BKV-sp immune defence,levels of BKV-sp CD4+ Tcells may represent the risk of florid PVAN and optimize individual timing of therapeutic interventions.

PS1-THU-040

Factors related to renal function in children with acute gastroenteritis

G. Milani* ¹, L. Castellazzi¹, M. Mazzoni¹, C. Persico¹, P. Grillo², E. Laicini¹, A. Rocchi¹, L. Dell’Era¹, A. Vettori¹, E. Fossali¹

¹Emergency Department, De Marchi Clinic, Foundation IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy, ²Epidemilogy Department, Foundation IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

In course of gastroenteritis, renal perfusion and GFR can decrease secondary to extracellular volume depletion .When GFR becomes less than 80 ml/min/m2 it is considered index of renal failure.The aim of this study is evaluating factors related to renal function in children with acute gastroenteritis. We analyzed retrospectively 110 patients with acute gatroenteritis in our pediatric emergency department in the period from the first of january 2009 and 31th of april 2009. We evaluate the main clinical parametres (age, refill, neurological state, episodes of vomiting and diarrhoea, diuresis) in relation to kidney function. In multivariant analysis we found that glomerular filtration has a direct correlation with the age of the children and it has resulted the only significant prognostic factor, which we considered for GF in our sample.For second, clincial parametres we considered can be correlated for about the 44% of the variability of GFR in pediatric gastroenteritis. In conclusion age of patients is an useful prognostic index of kidney filtration function in course of gastroenteritis.

PS1-THU-041

Nutcracker syndrome and idiopathic immunoglobulin a nephropathy: case report and review of the literature

M. Mazzoni* ¹, C. Persico¹, R. Celano¹, A. Edefonti², E. Laicini¹, G. Bertolozzi¹, G. Milani¹, F. Stefanini¹, M. Bianchetti³, E. Fossali¹

¹Emergency Unit, Clinica Pediatrica De Marchi, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, ²Pediatric Nephrology and Dialysis Unit, Clinica Pediatrica De Marchi, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, ³Division of Pediatrics, Mendrisio and Bellinzona Hospitals, and University of Bern, Switzerland

In course of gastroenteritis, renal perfusion and GFR can decrease secondary to extracellular volume depletion .When GFR becomes less than 80 ml/min/m2 it is considered index of renal failure.The aim of this study is evaluating factors related to renal function in children with acute gastroenteritis. We analyzed retrospectively 110 patients with acute gatroenteritis in our pediatric emergency department in the period from the first of january 2009 and 31th of april 2009. We evaluate the main clinical parametres (age, refill, neurological state, episodes of vomiting and diarrhoea, diuresis) in relation to kidney function.In multivariant analysis we found that glomerular filtration has a direct correlation with the age of the children and it has resulted the only significant prognostic factor, which we considered for GF in our sample.For second, clincial parametres we considered can be correlated for about the 44% of the variability of GFR in pediatric gastroenteritis. In conclusion age of patients is an useful prognostic index of kidney filtration function in course of gastroenteritis.

PS1-THU-043

Management of BK viremia and nephropathy in pediatric renal transplant recipients with intravenous immunoglobulin

E. Anyaegbu* ¹, P. Hmiel¹

¹Washington University in St Louis, Missouri, USA

BK nephropathy (BKN) has become of significant concern as a cause of graft dysfunction and loss in the renal transplant population. Latent BK virus is reactivated in the setting of immunosuppression (IS), causing tubulointerstitial nephritis in up to 5% of patients. Standard therapy for Bk viremia and nephropathy has not been established.

We report our successful treatment of BK viremia and nephropathy with IS reduction and administration of IVIg.

85 patients received a renal transplant between 2000 and 2010. Screening for BK virus was done for elevations in serum creatinine (SCr). 4.7% and 2.3% had BK viruria and viremia respectively. One patient developed BK viremia following therapy for acute rejection. He had persistent BK viremia following reduction of IS and received 5 doses of IVIg at 0.5 g/kg with viral clearance. SCr peaked at 2.2 mg/dl and was down to 1 mg/dl with viral clearance. Another patient was found to have BKN on biopsy. His SCr increased to 1.5 mg/dl at viral detection from his baseline of 07–0.9 mg/dl. IS was reduced and he received 6 doses of 0.5 g/kg IVIg monthly with clearance of BK viremia and improved allograft function.

Viral clearance with improvement of allograft dysfunction was seen in all our patients. The therapeutic benefit of IVIg after an inadequate response to reduction in IS was seen. Our report shows that reduction in IS with development of BK viremia and administration of IVIg for treatment of rising viremia and BKN is efficacious. We speculate that reduction in IS and administration of IVIg with persistent BK viremia and nephropathy is a therapeutic option to the rising threat of BKN.

PS1-THU-051

Cephalosporin induced non-convulsive status epilepticus in two patients with renal failure

B. Yildiz* ¹, N. Kural¹, A. Yakut², N. Cetin¹

¹Eskisehir Osmangazi University, Faculty of Medicine, Department of Pediatric Nephrology, Eskisehir, Turkey, ²Eskisehir Osmangazi University, Faculty of Medicine, Department of Pediatric Neurology, Eskisehir, Turkey

Non-convulsive-status-epilepticus (NCSE) is defined as altered consciousness status without clinical convulsive signs where epileptic discharges are detected in EEG. We here report cephalosporin-related NCSE with accompanied by a change in consciousness, minimal myoclonus and diffuse triphasic spikes and slow wave activity on EEG in two patients with renal failure. Case I: 15-year-old girl on CAPD therapy for end-stage-renal-disease (ESRD) secondary to VUR was admitted due to peritonitis. She was treated with ceftazidime (IV and IP route). The doses were modified according to the recommended outlines in renal failure patients. On the 5th day of therapy, she developed head ache, vomiting, confusion and minimal myoclonus involving on hands. Case II: 7 years old girl who diagnosed ESRD secondary to VUR was admitted due to pneumonia. She was treated with cefepime which is modified renal dose. On the 15th day of therapy, she developed confusion and minimal myoclonus. In two cases, the rest of the physical examination and cranial tomography findings was normal; laboratory tests showed no difference from routine policlinic follow-up; EEG revealed diffuse triphasic spikes and slow wave activity. The NCSE was thought to be related to ceftazidime and cefepim therapy. Ceftazidime and cefepim therapy was discontinued and valproic acid treatment was started. The neurological findings dramatically improved after in two days and EEG returned to normal after 10 and 7 days respectively. The mechanism of cephalosporin-induced-NCSE appears to be GABA-A receptor blockade that is leads to electrical excitability in neurons which in turn, can cause NCSE. In conclusion, NCSE may be occurring even in the presence of recommended renal failure dose. Measurement of serum concentrations can probably prevent NCSE during cephalosporin therapy. EEG should be a part of investigations in patients with ESRD receiving antibiotics.

PS1-THU-054

Anti-neutrophil cytoplasmic antibody (ANCA)-accociated vasculitis in childhood: clinical/histological features and long-term outcome

E. Siomou* ¹, D. Tramma¹, C. Bowen², D. Milford¹

¹Depatment of Nephrology, Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, UK, ²Department of Paediatric Pathology, Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, UK

Objectives and study: To analyze the clinical/histological features and outcome in children with ANCA-associated vasculitis.

Methods: Cases of ANCA-associated vasculitis in children, diagnosed in our Hospital during the last 13 years (1/1998–12/2010) were studied retrospectively.

Results: Thirteen children, mean age 13.2 ± 2.9 years, were indentified. Six had microscopic polyangitis (MPA) and 7 Wegener granulomatosis (WG). Eleven had extrarenal involvement. All had acute nephritic syndrome at presentation, 11/13 had renal failure (6/6 with MPA and 5/7 with WG). Nephrotic range proteinuria was present in all with MPA and in 4/7 with WG. Renal biopsy revealed pauci-immune necrotizing glomerulonephritis (12/13). All but one with MPA and 4/7 with WG had crescents in 57–95% and 47–80% of the glomeruli respectively. Global sclerosis was seen in all with MPA and 3/7 with WG. Initial therapy consisted of methylprednisolone pulses, cyclophosphamide intravenously and plasma exchanges (9/13). All achieved early remission of extrarenal symptoms. All patients with normal urine output at presentation and few sclerotic glomeruli had normal renal function/no proteinuria (1 with MPA and 2 with WG) on follow-up. Chronic renal disease (CKD) stage II was noted in 4 (all with WG) and stage III–IV in 3 (all with MPA). Three patients developed end stage renal disease. Among them, 2 MPA had a severe presentation with GFR <15 ml/min/1.73 m², oliguria, nephrotic range proteinuria, crescents in 67–69% and global/subglobal sclerosis in 51–58% of the glomeruli.

Conclusions: A higher prevalence of WG was found than previously reported. WG had a better outcome than MPA. Risk factors at presentation for CKD were GFR <15 ml/min/1.73 m², oliguria, nephrotic range proteinuria, crescents and sclerotic glomeruli.

PS1-THU-056

Current guidelines for the management of chronic dialysis in children: a systematic review

N. Schoenmaker* ¹, M. Tromp¹, H. van der Lee², M. Offringa², J. Groothoff¹

¹Department of Pediatric Nephrology, Emma Children’s Hospital AMC, University of Amsterdam, Amsterdam, The Netherlands, ²Department of Pediatric Clinical Epidemiology, Emma Children’s Hospital AMC, University of Amsterdam, Amsterdam, The Netherlands

Objectives and study: Clinical practice guidelines aim to improve the quality of care, e.g. the management of chronic dialysis in children. However, for clinicians it is not always clear whether the quality of these guidelines is sufficient and whether the recommendations are based on evidence. The aim of this systematic review is to identify all current published guidelines for the management of chronic dialysis in children, assess the quality of their development, and appraise the evidence on which the recommendations are based.

Methods: A search strategy was developed using search terms related to chronic dialysis in children. Guidelines that were identified were reviewed by four reviewers independently, using a data extraction form containing 26 questions derived from the Appraisal of Guidelines for Research and Evaluation (AGREE) Collaboration instrument. We determined which of the recommendations were based on empirical evidence.

Results: Seventeen guidelines concerning 7 topics were identified, containing 369 recommendations. None of the guidelines met all criteria of the AGREE instrument, 10 guidelines met less than half of the criteria. Seven recommendations were based on randomized control trials (RCTs) in children, 4 on adult RCTs, 7 on cohort studies in children, 5 in adults, and 346 (94%) on expert opinion or consensus.

Conclusions: The development process of most of the guidelines for the management of chronic dialysis in children is poor, and recommendations are insufficiently based on evidence. International collaboration is needed to conduct the much needed RCTs and cohort studies, and for developing management guidelines.

PS1-THU-062

N-terminal fragment of pro-brain natriuretic peptide (NT-ProBNP) is better marker of ventricular dysfunction than left ventricular mass (LVM) in children undergoing dialysis

A. Alonso* ¹, C. Peralta¹, J. Rivas², C. G. Meseguer¹, C. Fernández¹, L. Espinosa¹, M. Navarro¹

¹Pediatric Nephrology Department, Hospital La Paz, Madrid, Spain ²Pediatric Cardiolgy Department, Hospital La Paz, Madrid, Spain

Objectives and study: NT-ProBNP is an independent marker of fluid overload, myocardial damage, morbidly and mortality in adult population on dialysis; however, blood accumulation in renal insufficiency makes difficult its interpretation. Isolated studies in children have shown a relationship with increase of LVM. The aim of this study is to evaluate the predicting value of ventricular systolic or diastolic dysfunction in children on dialysis.

Patients: 15 children on hemodialysis (6)or peritoneal dialysis(9) aged 9.48 ± 5 years were studied. The follow up on dialysis was 27 ± 31 months. Hypertension was found in 66%, left ventricular hypertrophy (LVH) in 46% and ventricular dysfunction in 33%. 60% of the patients had some type of cardiovascular event: acute lung oedema, cardiac insufficiency or hypertensive emergency.

Results: We found higher LVM in hypertensive patients 107 ± 66 versus 48 ± 13 gr/m2; Z score: 2.2 versus −1.44). Hypertensive patients had higher levels of NT-proBNP: 14407 ± 14000 versus 4423 ± 5084 pg/ml and troponin i: 0.11 ± 0.2 versus 0.03 ± 0.1 ng/ml. Relative risk [RR] of ventricular dysfunction were increased in patients with NT-ProBNP levels higher than 5500 pg/ml [RR = 2.5]. Previous cardiovascular events [RR = 2.5] and LVH [RR = 2] were also associated with ventricular dysfunction. We did not find any relationship between NT-proBNP levels and gain of weight among dialysis sessions, hypotension episodes, residual renal function, primary disease, modality and dose of dialysis, haemoglobin or PTH.

Conclusions: NT-ProBNP values higher than 5500 pg/ml are markers of myocardial dysfunction in children on dialysis.

PS1-THU-063

Utilization of hemofiltration for the treatment of life threatening tumor Lysis syndrome in pediatric Burkitt’s lymphoma. Presentation of 2 cases

O. Teslariu* ¹, M. Munteanu^{1, 2}, I. Crenguta Miron^{1, 2}, S. Dumitras¹, O. Brumariu¹

¹St. Mary Children’s Hospital, Iasi, Romania, ²University of Medicine and Pharmacy Gr. T. Popa, Iasi, Romania

Aim: Tumor Lysis Syndrome (TLS) represents a severe/ life threatening condition, complicating the initial phase of chemotherapy (CH) for giant, fast growing malignant tumor in children; commonly occurs in non-Hodgkin’s lymphomas and acute lymphocytic leukemia. The syndrome is manifesting by dramatic increase of urea, hypokalemia, arrhythmia, hyperuricemia, hypocalcaemia and acute renal failure; any delay in the treatment of TLS is complicated with high mortality. We have assessed the efficacy of hemofiltration based of 2 cases successfully treated with initial hemofiltration.

Material and methods: Case No 1: 13 years old boy with massive cervico-mediastinal Burkkit’s lymphoma; 24 hrs after initial CH (BFM-ICC 2002) he developed severe TLS: anuria, hypertension, high urea and creatinine, abnormality on ECG. He was treated immediately with continuous veno-venous hemofiltration (CVVH). 6 hours post hemofiltration he significantly improved and restart CH 5 days later; he is free of disease with normal kidney function for 3 years. Case No.2: 4 years old boy with massive tumor of the jaw; 2nd day after biopsy shows Burkkit’s lymphoma. Without any CH, he developed a typical picture of severe TLS with anuria. The CVVH was started immediately with significant improvement and good diuresis; he started CH after 72 hours and had a favorable outcome, free of disease for 2 years.

Results: In both cases the hemofiltration was very effective with no additional medical treatment. In both cases the venous access was via femoral vein. The hemofiltration utilized as CRRT has been performed with Aquarius TM machine (Edwards) and Polyethersulfona filters, type Aquamax. CONCLUSIONS: Early utilization of veno-venous hemofiltration in severe cases of TLS proved to be an effective tool, reversing the renal function to normal, allowing restarting the chemotherapy.

PS1-THU-069

Shigatec: a Phase II study assessing monoclonal antibodies against Shiga toxin 1 and 2 in Shiga toxin-producing E. coli-infected children

C.M. Taylor* ¹, M. Bitzan², D. Reymond³

¹Birmingham Childrens Hospital, Birmingham, UK, ²Montreal Children’s Hospital, Montreal, Canada, ³Thallion Pharmaceuticals Inc, Montreal, Canada

Background: Diarrhoea-associated haemolytic uremic syndrome (HUS) is the leading cause of acute kidney injury in children and Shiga toxin-producing E. coli (STEC) are the main pathogens responsible for causing HUS. There are no approved therapies to prevent the development of HUS or its associated complications, only supportive care. Shigamabs, comprised of monoclonal antibodies against Shiga toxin 1 and Shiga toxin 2, has been shown active in preclinical models and well tolerated in four Phase I studies in healthy adults.

Methods: A randomized, double blind, placebo controlled Phase II study was initiated on November 26, 2010. Thirteen clinical centers in South America are enrolling children 6 months to 18 years of age presenting with bloody diarrhea. The study consists of two arms: A) standard of care + Shigamabs, or B) standard of care + placebo. Following a diagnosis of STEC infection using two commercial diagnostic kits and randomization (2:1), Shigamabs or placebo is infused over one hour as a single infusion. Two doses are being tested in two sequential cohorts of 21 patients each: 1) a low-dose cohort receiving 1 mg/kg of each antibody; and 2) a high-dose cohort receiving 3 mg/kg of each antibody. The study consists of a core phase (first two months post-infusion), and an extension phase (up to 12 months post-infusion). The primary endpoints are safety and tolerability; secondary endpoints efficacy and pharmacokinetics.

Results: In three months, 305 patients have been screened and 22 patients have been enrolled in the low-dose cohort. The mean age was 3 ½ years with 68% of children less than 4 years.

Conclusions: SHIGATEC is the first clinical study testing Shigamabs for its safety and potential benefits in the prevention of HUS and its complications in infected children. Screening and recruiting is progressing on time demonstrating the feasibility of this approach.

PS1-THU-076

Successful treatment of central nervous system (CNS) post-transplant lymphoproliferative disorder (PTLD) using rituximab and cranial radiotherapy (CR)

V. Said Conti* ¹, P. Amrolia², M. Gaze³, S. Stoneham⁴, R. Shroff¹, S. Marks¹

¹Nephrology, Great Ormond Street Hospital, London UK, ²Molecular Immunology, Institute of Child Health, London UK, ³Clinical Oncology, University College Hospital/Great Ormond Street Hospital, London UK, ⁴Paediatric Oncology, University College Hospital, London UK

Various modalities of treatment have been put forward for the treatment of Ebstein-Barr virus (EBV)-driven CNS PTLD including reduction of immunosuppression, CR, intravenous and intrathecal rituximab when CD20 is expressed on B-lymphocytes and PTLD cells.

We report the successful treatment of EBV-driven CNS PTLD by reduction in immunosuppression, CR and intravenous rituximab. An 11-year old boy with a living-related renal transplant for end-stage renal failure secondary to posterior urethral valves and bilateral renal dysplasia and on triple immune suppression with prednisolone, tacrolimus and azathioprine had a rising EBV load which was managed with reduction in tacrolimus dose to achieve low levels, withdrawal of azathioprine and introduction of MMF. He presented 6 years post-transplant with a seizure and abnormal neurology secondary to polymorphous hyperplastic lesions in the brain.

He required ventilation for his depressed neurological state and intravenous antibiotics until culture-negative. A brain MRI and brain biopsy were suggestive of PTLD. MMF was stopped, prednisolone treatment intensified and he received a rituximab infusion followed by 15 sessions of CR. His allograft function remained stable throughout with creatinine at his baseline of 120 mol/l. Prior to this presentation his EBV count had fluctuated between 1000 copies up to 6 million copies/ml whole blood and they were high in both his cerebrospinal fluid and blood at this time. He made an excellent neurological recovery with some residual speech impairment but with negative EBV viral load in his blood and almost complete resolution of his brain lesions on MRI within two months from treatment.

We illustrate a case of EBV-driven CNS CD-20+ PTLD which responded to reduction in immunosupression, rituximab and CR. He remains well on immune suppression with prednisolone only and supportive treatment for chronic kidney disease.

PS1-THU-077

Preservation of renal allograft function despite peri-operative hypotension resulting in cervical cord ischaemia and recoverable quadriparesis

V. Said Conti* ¹, P. Prabhakar², S. Marks¹

¹Nephrology, Great Ormond Street Hospital, London UK, ²Neurology, Great Ormond Street Hospital, London UK

Maintaining good renal allograft perfusion is always advocated in renal transplant recipients (RTR) especially early post-transplant and during subsequent operations.

We report how minimal acute tubular necrosis occurred in a RTR post-laparotomy for proctectomy and ileoanal pouch formation with peri-operative hypotension that caused ischaemic injury at the cervical spinal cord level of C2-C6 with resultant quadriplegia. A 17-year old young man with a living-related renal transplant for end-stage renal failure secondary to posterior urethral valves, bilateral renal dysplasia and vesico-ureteric reflux, who had scoliosis and a colectomy and ileostomy for eosinophilic colitis, underwent epidural anaesthesia and had intraoperative hypotension.

Post-operatively he required 100 ml/kg fluid resuscitation and vasopressors to maintain adequate blood pressure and renal allograft perfusion which resulted in him being ventilated for pulmonary oedema. His allograft function deteriorated with a rise in his plasma creatinine from a baseline of 134 to 168 μmol/L and trough tacrolimus level of 7.6 mcg/L. After improvement in blood pressure to 112-128/60–90 mmHg, a furosemide infusion was started for his pulmonary oedema to maintain urine output of 3 mls/kg/hr. Ultrasound showed a well-perfused allograft and a known bladder calculus. Day 6 post-operatively, his allograft function had returned to baseline but he complained of paraesthesia in his hands and feet which progressed to generalized weakness and lack of sensation. MRI scan showed a cervical intramedullary lesion from C2–C6 without cerebrovascular accident or spinal compressive lesions. Despite a guarded neurological prognosis, he has made good progress with stable renal allograft function.

This degree of hypotension is expected to be associated with a greater extent of acute tubular necrosis and renal allograft dysfunction. He subsequently underwent closure of his ileostomy and removal of the bladder calculus without neurological sequelae.

PS1-THU-083

Pleurodesis treatment with tetracycline in peritoneal dialysis-complicated hydrothorax

O. Durmaz* ¹, O. Dönmez¹

¹Uludag University Faculty of Medicine, Department of Pediatric Nephrology, Bursa, Turkey

Pleuroperitoneal communication is a complication of continuous ambulatory peritoneal dialysis (CAPD) that can necessitate cessation of CAPD. Hydrothorax as a result of pleuroperitoneal communication occurs in approximately 2% of CAPD patients. Herein, we report a hydrothorax case that occured during CAPD and highligthen the problems in diagnosis and management of this condition. A 5 year-old boy with focal segmental glomerulosclerosis was started on CAPD as he reached end-stage renal failure. One month later, he presented with a history of shortness of breath on exertion and dry cough increasing in supine position. In thorocentesis, the pleural fluid was clear with glucose level of 114 mg/dl (blood sugar was 68 mg/dl), protein of 10 g/L (normal 10–20 g/L), lactic dehydrogenase level of 108 μ/L (normal 50–195 μ/L). The white cell count of pleural fluid was 250 cells/ml. The fluid culture was sterile and no malignant cells were detected. Pleurodesis with tetracycline was twice performed, CAPD theraphy was discontinued and he was switched to haemodialysis therapy for three a week. The pleural effusion subsided and has not recurred for following two years.

PS1-THU-084

The frequency of renal osteodysthrophy in children with chronic renal failure and the association of renal osteodtstrophy with biochemical parameters

O. Durmaz* ¹, O. Dönmez¹

¹Uludag University Faculty of Medicine, Department of Pediatric Nephrology, Bursa, Turkey

A total of 20 children who were started on peritoneal dialysis treatment due to chronic renal failure between August 1997 and January 2010 and who were followed up at outpatient clinic between January 20, 2010 and February 10, 2010 were included to this study.

Nine (45%) of the children were male, 11 (55%) of them were female and the mean duration of peritoneal dialysis was 3.54 ± 2.2 years When bone mineral density (BMD) of our patients were compared with gender and age matched healthy children, BMD was found to be low in 15 patients (75%). Osteopenia and severe osteopenia was determined in 9 (45%) and 6 (30%) patients, respectively. The mean BMD was 0.70 ± 0.22 g/cm2, the mean Z score was −1.86 ± 1.91. When duration of follow-up and gender were compared with BMD and Z scores, no significant differences were determined. When the association between Z score and biochemical parameters were evaluated, no significant differences were found between Ca, ALP levels and Z score. In contrast, there was a significant correlation between CaxP, PTH and P levels and Z score. The mean Kt/V levels were 2.32 ± 0.82. Kt/V were higher than 2 in 13 patients (65%) and lower than 2 in 7 patients (35%). DEXA score was lower than −1 (osteopenia and/or severe osteopenia) in 6 of the 7 patients (85%) with a Kt/V level lower than 2. DEXA scores were significantly lower in patients whose Kt/V levels were lower than 2.

Conclusion: In this study, biochemical parameters such as CaxP below 55, P above 7 mg/dl, PTH above 200 pg/mL and Kt/V below 2 was shown to be independent risk factors for development of ROD. We suggest that biochemical parameters and DEXA must be performed from the third stage of ESKD for the prevention and early determination of ROD.

PS1-THU-092

Intra-patient variability in tacrolimus trough levels does not correlate with renal function decline in paediatric renal transplant recipients

A. Prytula* ¹, A. H. Bouts², R. A. A. Mathot³, W. C. J. Hop⁴, T. van Gelder⁵, K. Cransberg¹

¹Department of Pediatric Nephrology, Erasmus Medical Center- Sophia Children’s Hospital, Rotterdam, The Netherlands, ²Department of Pediatric Nephrology, Emma Children’s Hospital, Amsterdam, The Netherlands ³Department of Clinical Pharmacy, Academic Medical Center, Amsterdam, The Netherlands, ⁴Department of Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands, ⁵Hospital Pharmacy, Erasmus University Medical Center, rotterdam, The Netherlands

Objectives: High intra-patient variability in tacrolimus (TCL) clearance is a risk factor for allograft loss and late acute rejection in renal transplant recipients. We hypothesized that a higher intra-patient variability leads to a faster decline in glomerular filtration rate (GFR) in paediatric renal transplant patients.

Methods: We included 69 children who had undergone renal transplantation between April 1996 and May 2009 in two paediatric nephrology centres in the Netherlands. We analysed TCL trough levels over a period of one year commencing at least three months after the introduction of TCL. All TCL levels were adjusted accordingly if the time elapsed between drug ingestion and level measurement exceeded 12 hours. TCL levels variability was expressed as variability coefficient (VC). We investigated the correlation between the VC and the decline in GFR over two years (∆GFR), estimated using the Schwartz formula.

Results: Four children experienced graft loss during the study period. The adjusted mean trough TCL level was 6.6 (±2.0) ng/ml. The mean intra-patient variability in TCL clearance was 32.9% (range 8.6–77.6%). The mean ∆GFR in the first year of follow-up was −1.9(±15.48) ml/min/1.73 m² and over two years −4.4(±14.54) ml/min/1.73 m². There was no correlation between the intra-patient variability in TCL levels and ∆GFR after one and two years of follow-up neither for the whole study population (Spearman’s rho 0.066 and 0.028, respectively) nor in children with mean TCL trough levels between 4 and 8 ng/ml (Spearman’s rho 0.122 and 0.044).

Conclusions: We found no correlation for intra-patient variability in TCL clearance with accelerated decline in GFR during a 2 year follow-up period in our study population.

PS1-THU-099

Epidemiology of chronic kidney disease in children in Serbia

A. Peco-Antić* ^1,2, R. Bogdanović^1,3, D. Paripović², A. Paripović³, N. Kocev⁴, E. Golubović⁵, B. Milošević⁶

¹Medical Faculty of University of Belgrade, Belgrade, Serbia, ²University Children’s Hospital, Belgrade, Serbia, ³Instite for Mother and Child Health, Belgrade, ⁴Institute for statistics, Medical Faculty of University of Belgrade, Belgrade, Serbia, ⁵Medical faculty of University of Nis, Nis, Serbia, ⁶Medical faculty of University of Novi Sad, Novi Sad, Serbia

Serbian Pediatric Registry of Chronic Kidney Disease (SPRECKID) was established in 2000 to collect data on incidence, prevalence, etiology, treatment modalities and outcome of children with non-terminal (CKD 2–4) or terminal (CKD 5) chronic kidney disease. All of the Serbian centres potentially involved in caring of children and adolescents with CKD were invited to report index cases. During 10-year, 336 children were registered (211 boys, 125 girls, male/female ratio 1.7). The median age at registration was 9.0 years (interquartile range, IQR 3–13). Median follow-up of the patients in registry was 4.0 years (IQR, 1–9). The median GFR at the time of the registration was 39.6 ml/min/1.73 m², (IQR, 13.8–65.4). At the entry in the study 104 (31.0%) patients were in CKD stage 2, ninety (26.8%) in CKD stage 3, forty five in (13.4%) CKD stage 4, and 97 (28.9%) were in CKD stage 5. Median annual incidence of CKD 2–5 stage was 14.3 per million age related population (pmarp), while those of CKD 2–4 or CKD 5 were 9.1 pmarp and 5.7 pmarp, respectively. The median prevalence of CKD 2–5 was 96.1 pmarp, 52.8 pmarp in CKD 2–4 and 62.2 pmarp in CKD5. The main causes of CKD were CAKUT and hereditary nephropathies. Kidney survival was the worst in children with glomerular diseases and in those with advanced CKD. Hemodialysis was the most common as the first modality of renal replacement therapy (RRT). Conclusion: Incidence, prevalence and etiology of pediatric CKD in Serbia are similar to those reported from developed European countries. In contrast to RRT from these countries, hemodialysis was preferred mode of RRT for children in Serbia. Mortality rate was 4.5%, mainly due to cardiovascular and infectious complications.

PS1-THU-100

Peritonitis in children on peritoneal dialysis in Spain: influence of biocompatible peritoneal solutions

A. Alonso* ¹, A. Sanchez², M. Sanahuja³, G. Ariceta⁴, D. Morales⁵, R. Muley⁶, J. Camacho⁷, F. Santos⁸, M. Gil⁹

¹La Paz Hospital, Madrid, Spain, ²Virgen Rocío Hospital, Sevilla, Spain, ³La Fe Hospital, Valencia, Spain, ⁴Cruces Hospital, Bilbao, Spain, ⁵Gregorio Marañón Hospital, Madrid, Spain, ⁶Doce Octubre Hospital, Madrid, Spain, ⁷San Juan de Dios Hospital, Barcelona, Spain, ⁸Central de Asturias Hospital, Oviedo, Spain, ⁹Xeral Hospital, Santiago, Spain

Rationale and objectives: Peritonitis is a frequent complication of children on peritoneal dialysis (PD). Our objective is to verify if biocompatible dialysis solutions have a positive effect on peritonitis in Spanish children on PD.

Patients: 184 children receiving PD from 2003 to 2009 were recruited by PAEDIATRIC PERITONEAL DIALYSIS SPANISH STUDY GROUP. Median age at onset was of 7.4 years (20% younger than 2 years). Mortality was 3% and PD survival 88%. PD failure was attributed to peritonitis in one third of patients. Bicarbonate/lactate-buffered solutions in 63% of patients; icodextrin in 42% and amino acids in 16% were used.

Results: The overall peritonitis rate was 1/17 patient-months. 95% of episodes cured without catheter removal. Recurrence was present in 10% of episodes. Children under two years had the highest incidence: 1/12 patient-months episodes. Etiologic agents were: Gram negative (22%); Staph. coagulase negative (17%); Staph. aureus (13%); Pseudomonas (13%); Gram positive (14%); Unknown (9%); Fungal peritonitis (1.8%). Pseudomonas and Staph. aureus peritonitis were associated with higher risk of recurrence. Pseudomonas and fungal peritonitis had the highest number of cloudy effluent days: 5.25 ± 4 versus 2.27 ± 2. Factors associated with peritonitis were: Young age, gastrostomy; exit catheter infection, loss of residual function and low weight at onset. Peritonitis rate was similar in patients treated either bicarbonate or lactate-buffered; however; icodextrin and amino-acid-containing solutions in combination decreased peritonitis rate: 0.8 ± 0.09 versus 1.3 ± 1.3 episodes per patient.

Conclusions: The Spanish children on PD have an acceptable rate of peritonitis. Bicarbonate buffered solutions does not improve incidence but icodextrin and amino-acid-containing solution in combination have a positive effect.

PS1-THU-101

Successful combined liver and kidney transplantation in a child with hypocomplementemic atypical haemolytic uremic syndrome (aHUS) due to a factor B mutation

A. Alonso* ¹, M. Melgosa¹, M. López Trascasa², M. Navarro¹, A. Vega³, P. Sánchez Corral²

¹Pediatric Nephrology Department. Hospital La Paz, Madrid, Spain, ²Immunology Department Hospital La Paz, Madrid, Spain, ³Pediatric Hepatology Department. Hospital La Paz, Madrid, Spain

Case description and follow up: A four-month old boy was diagnosed of hypocomplementemic aHUS on May 2000, and during the following three years he suffered eight recurrences of the disease. He developed a severe hypertension requiring more than 5 anti-hypertensive drugs, and presented acrocyanosis, urticarial-like phenomena and several confusional episodes secondary to his microvascular disease. Plasma infusion or exchange, and immunosuppressive treatments did not improve the clinical evolution of the patient, who developed end stage renal disease at the age of 3 years. Hypertension and vascular symptoms persisted while he was on peritoneal dialysis or hemodialysis, as well after bilateral nephrectomy. Complement C3 levels remained very low, while C4 levels were normal. No mutations were found in the complement components factor H, factor I or MCP, but the patient presented a heterozygous gain-of-function mutation in factor B (Lys323Glu; Goicoechea et al. 2007; PNAS 104: 240–245).

A combined liver and kidney transplant was performed on March 2009. Kidney and liver functions normalized in the first two weeks. C3 and C4 levels were low the first week, but the C3/C4 ratio was completely normal immediately after transplantation, indicating that the anomalous C3 activation has been corrected. The patient has remained stable for 12 months without new HUS relapses.

Conclusions: The good clinical outcome of the patient since liver-renal transplantation suggest that this could be a good therapeutic option for patients presenting atypical HUS associated to mutations in factor B.

PS1-THU-104

Hyperuricemia in pediatric renal transplant recipients

A. Uslu Gökceoglu* ¹, C. S. Dogan1, E. Comak¹, A. E. Kuyubulu¹, M. Koyun¹, S. Akman¹

¹Akdeniz University Medical Faculty, Department of Pediatrics, Division of Pediatric Nephrology, Antalya, Turkey

We aimed to evaluate the prevalance and relevant clinical variables of hyperuricemia in pediatric renal transplant recipients with intact graft function.

In this retrospective study, pediatric allograft recipients, who had renal transplantation between April 2005–April 2010, with an estimated GFR >60 ml/min were evaluated. Serum uric acid (UA) levels were measured every 2 and 3 months in patients during post-transplant 6–12 months and after 12 months, respectively. Each patient’s UA level was obtained by averaging all UA measurements obtained during the follow-up period except for post-transplant first 6 months. The upper limits of serum UA levels were regarded as 5.9, 6.4 and 7.2 mg/dl in children aged 2–12 years, in 12–14 year-olds and females >14 yr, and in males >14 yr, respectively.

49 children, 30 boys, with a mean age of 14.4 ± 3.9 years (range: 3.5–20 years), were included. The median duration after tx was 26 months (range: 10–69). Mean serum UA levels were 4.7 ± 1.1 mg/dl. Only three (6%) of all patients had hyperuricemia. There was a significant correlation between mean UA concentration and both serum creatinine (r = 0.583) and cystatin C (r = 0.481). Also, there was an inverse correlation between GFR and serum UA (r = −0.283). No significant correlation was found between mean serum UA concentration and presence of hypertension, time span post-transplantation and body mass index, as well as serum calcium, phosphorus, albumin, triglyceride, cholesterol, blood glucose and magnesium. Serum UA concentrations and the frequency of hyperuricemia were similar in patients receiving CsA and tacrolimus.

Hyperuricemia is infrequent in pediatric renal allograft recipients with intact graft function.

PS1-THU-105

Bad sleep quality in pediatric renal transplant recipients

A. Uslu Gökceoglu* ¹, C. S. Dogan¹, E. Comak¹, A. E. Kuyubulu¹, M. Koyun¹, S. Akman¹

¹Akdeniz University Medical Faculty, Department of Pediatrics, Division of Pediatric Nephrology, Antalya, Turkey

We aimed to evaluate the frequency of sleep disorders in children with renal transplantation. Children aged >6 years who had at least 3 months follow-up after transplantation were included in the study. Pittsburg Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were introduced to the patients. The results of PSQI were inspected as seven variabilities: subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance, day dysfunction due to sleepiness and any need of medication for sleep. Bad sleep quality was defined as a total PSQI score >5. Day dysfunction due to sleepiness was defined as ESS score >10.

A total of 28 children, 15 girls, aged 15.3 ± 2.8 years (9.5–20) were included in the study. The median post-transplant period was 22.7 months (3–127). Mean hemoglobin level was 12.6 ± 1.7 mg/dl and eGFR was 76.8 ± 23.3 ml/min/1.73 m². Of all patients, 39% had bad sleep quality; however, only 3 patients (%10) thought that their sleep quality was bad. Sleep latency of 21 patients was less than 30 minutes. Sleep duration was less than 6 hours in 2 patients. Sleep efficiency of 3 patients was less than 85%. Day dysfunction due to sleepiness was 52% in PSQI and 4% in ESS. Only three patients did not suffer from any sleep disturbances. No statistically significant correlation was found between hemoglobin levels and total score of PSQI. Although statistically insignificant, there was a negative correlation between post-transplant period and total PSQI score (r = −0.168, p = 0.39).

Conclusion: A high incidence of sleep disturbances exist in children with renal transplantation.

PS1-THU-110

MMF associated alopecia: a case report

B. Kasap* ¹, C. Alparslan², A. Bal², T. Çelik², Ö. Yavaşcan¹, N. Aksu¹

¹Tepecik Research and Training Hospital Division of Pediatric Nephrology, Izmir, Turkey, ²Tepecik Research and Training Hospital Department of Pediatrics, Izmir, Turkey

Introduction: Mycophenolate mophetil (MMF) is an immunosuppressive more recently used in patients with steroid resistant and steroid dependant nephrotic syndrome. The most common side effects are gastrointestinal disturbances (gastritis, nausea, vomiting, dyspepsia, constipation, diarrhea and abdominal distention), anemia, leukopenia, predisposition to infection and malignancies. Alopecia is an infrequent side effect. Here, we report a patient in whom scarsity in hair volume has been realized after MMF treatment.

Case report: The patient had her first nephrotic syndrome attack when she was 7 years-old and had a second one 6 months after the end of the treatment. At low dose steroid treatment, one year after the second attack, she had a third one. The biopsy revelaed mesangial proliferation and cyclosporine has been added to steroid treatment. Almost 30 months after CsA treatment she had a new relaps and the second biopsy revealed no toxic effect of CsA or findings suggestive of segmental sclerosis. The treatment protocol was ended at the end of 2 years. A month after cessation of the treatment, she had a new relapse. She was evaluated as steroid and CsA dependant and since the total CsA treatment duration reached 55 months, MMF was institituted with a dose of 1000 mg/m2. At the second month of MMF treatment, proteinuria level and the other laboratory parameters reached normal levels, but the patient recognized sparsity in her hair. The dose was decreased by 50%. A month later, hair loss was stopped and new hair appeared around the scalp. She remained in remission during the following 8 months.

Conclusion: This case has been reported to emphasize that MMF is an effective agent in steroid and CsA dependant nephrotic syndrome, and to draw attention to alopecia, an infrequent side affect of MMF.

PS1-THU-117

Pre-treatment of different dairy products and breastmilk with sevelamer hydrochloride and sevelamer carbonate to reduce phosphate

C. Schröder* ¹, R. Raaijmakers², L. Houkes², J. Willems², L. Monnens²

¹Gelre Hospital, Apeldoorn, The Netherlands, ²Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Objectives: Hyperphosphatemia and an elevated calcium x phosphate product predispose to metastatic calcifications, with increased risk of cardiovascular complications in patients with renal failure. Sevelamer hydrochloride and sevelamer carbonate are effective phosphate-binders in the gastro-intestinal tract. For children important practical disadvantages exist: sevelamer clogs nasopharyngeal tubes and can cause gastro-intestinal complaints. Pre-treatment of dairy products could solve this problem.

Methods: Sevelamer hydrochloride (800 mg tablets) and sevelamer carbonate (800 mg tablets or 800 mg powder) were suspended in different dairy products. Skimmed cow’s milk, breastmilk, standard baby formula and tube feeding formula were tested in different concentrations. After suspension the samples were stored for 10 minutes to allow for sevelamer to precipitate. The supernatant was collected and analyzed. Phosphate, calcium, magnesium, potassium, sodium, chloride and pH were determined.

Results: A significant decrease in phosphate content in all dairy products was observed. With sevelamer hydrochloride phosphate reduction was 48% to 90% for different products. With sevelamer carbonate phosphate reduction was 22% to 92%. The highest effectivity was found in breastmilk. An increase of pH was found in all products with both sevelamer hydrochloride and sevelamer carbonate. With sevelamer hydrochloride a significant increase in chloride occurred in all products as well. Calcium decreased especially in breastmilk.

Conclusions: Sevelamer hydrochloride and sevelamer carbonate can be added to different dairy products to effectively lower the phosphate content and thus avoid troublesome ingestion in children. The change in pH for sevelamer hydrochloride is remarkable and most likely reflects an interaction with buffering proteins, especially micelles in dairy products. The calcium decrease found with breastmilk has to be taken into consideration.

PS1-THU-119

Goodpasture syndrome in an 11-year-old girl

D. Kuzmanovska* ¹, E. Sahpazova¹, R. Jovanovic², G. Petrusevska²

¹Pediatric Clinic, Medical Faculty, St. Cyril & Methodius University, Skopje, Macedonia, ²Institut for pathology, Medical Faculty, St. Cyril & Methodius University, Skopje, Macedonia

Objectives: Goodpasture\’s syndrome is an autoimmune disease, frequently leading to severe deterioration of renal function. It has rarely been described in children, and data in the literature are primarily limited to case reports.

Methods: In this work we report young female with this rare disease.

Results: An 11-year-old girl developed picture of pulmonary hemosiderosis, rapidly progressive glomerulonephritis and advanced renal failure in the space of 10 days. By renal biopsy severe extracapillary glomerulonephritis was found with crescents in more than 90% of glomeruli. Circulating anti-glomerular basement membrane antibody was detected and linear deposition of IgG along glomerular basement membrane was observed. A diagnosis of Goodpasture\’s syndrome was made and treatment was started with prednisone, cyclophosphamide and periodic plasmapheresis with progressive but not complete disappearance of circulating anti-glomerular basement membrane antibody. After suspension of plasmapheresis despite immunosuppressive therapy, the child went into terminal renal failure. The natural history of the disease in this case and the results of treatment are discussed.

Conclusions: The diagnosis of Goodpasture\’s syndrome can be confirmed by the presence of circulating anti-GBM antibodies and/or deposition of anti¬bodies on the glomerular basement membrane demonstrated by immunofluorescent stai¬ning of the renal biopsy specimen. Management should be aggressive and started immediately upon suspicion. The presence of advanced renal failure at pre¬sentation and/or presence of crescents affecting more than 50% of glomeruli are a serious prog¬nostic sign.

PS1-THU-130

Congenital nephrotic syndrome due to maternal syphilis infection during pregnancy

E. Tudorache* ^1,2, J. Hogan¹, M. E. Dourthe¹, A. L. Sellier-Leclerc¹, T. Ulinski^1,2

¹Pediatric Nephrology, Armand Trousseau Hospital, APHP, Paris, France, ²Université Pierre et Marie Curie, Paris 6, France

Congenital syphilis is a rare disease in France, even if the numbers of cases increase since 2000 in western countries.

The rate of disease transmission to the foetus is from 70 to 100% in primary and untreated syphilis Fetal infection by Treponema Pallidum can occur at any time during the pregnancy but mostly after 16 weeks gestational age (GA).

We report a case of congenital syphilis with acute renal failure and nephrotic syndrome. TPHA/VDRL serology was negative at first exam at 10 weeks GA. At 34 weeks of gestation,ultrasound examination showed hydrops foetalis. The child was born at 35 weeks GA with septic shock, hepatosplenomegaly, and generalized blisters.

Initial blood analysis showed: haemoglobin 11 g/dL, thrombocytopenia 22.000/mm3 (despite intrauterine blood and platelets transfusion), CRP 233 mg/L, urea 4 mmol/L, serum creatinine 72 μmol/L, serum proteins 56 g/L, SGOT 482 UI/L, SGPT 224 UI/L. The limbs X-rays showed typical bones injuries such as irregular radius and ulna metaphyses.

The Treponema Pallidum infection was confirmed in the mother (despite negative serology in the first trimester of pregnancy) and the child. Peritoneal dialysis was required during the first month of life despite immediate adequate anti-syphilis antibiotic treatment. Mild chronic renal failure, mild arterial hypertension and a low grade proteinuria persisted at the age of six months.

Conclusion, additional surveillance of syphilitic serology during pregnancy after the first trimester can be of interest.

PS1-THU-131

Childhood onset diabetes mellitus post transplant in a girl with TCF2 mutation

E. Tudorache* ^1,4, A. L. Sellier-Leclerc¹, M. Lenoir², N. Tubiana³, T. Ulinski^1,4

¹Pediatric Nephrology, Armand Trousseau Hospital, APHP, Paris, France, ²Pediatric Radiology, Armand Trousseau Hospital APHP, Paris, France, ³Pediatric Endocrinology, Robert Debré Hospital, APHP,Paris, France, ⁴Université Pierre et Marie Curie, Paris 6, Paris, France

Heterozygous mutations of TCF2 have been associated with maturity onset diabetes of the young (MODY)-5, renal malformations, hyperuricemia, and occasionally internal genital malformations in female. We report a girl with bilateral renal hypodysplasia and de novo heterozygous TCF2 gene mutation associated to pancreas hypoplasia. Oral glucose tolerance test was normal before transplantation. At the age of nine years, she developed transient ketoacidosis immediately post transplant, temporarily requiring insulin. During glucocorticoid tappering, impaired glucose tolerance persisted. Cyclosporine A was switched to tacrolimus at 2 months post transplant for severe hypertrichosis and tacrolimus blood levels were in the normal range. Eight months post transplant CMV hepatitis developed requiring gancyclovir treatment. Overt insulin dependent diabetes mellitus developed one year post transplant. Pathogenic factors which might have played a role in the acceleration of diabetes were i/switch from cyclosporine to tacrolimus, ii/weight excess and iii/CMV infection. TCF2 analysis might therefore be of interest in pediatric and adult patients with congenital abnormalities of the kidney and the urinary tract (CAKUT) in order to improve post transplant management in terms of steroid and tacrolimus exposure.

PS1-THU-132

Different modulation of regulatory T cells by toll like receptor activation in primary IgA nephropathy and in Henoch-Schoenlein purpura nephritis: a factor regulating the different clinical outcome?

E. Loiacono* ¹, R. Camilla¹, L. Morando¹, L. Peruzzi¹, M. Conrieri², M. Bianciotto², F. M. Bosetti², R. Gallo¹, A. Amore¹, R. Coppo¹

¹Nephrology, Dialysis and Transplantation—Regina Margherita Hospital, Turin, Italy, ²Emergency Pediatric Department—Regina Margherita Hospital, Turin, Italy

Objectives and study: Primary IgA Nephropathy (pIgAN) and IgAN related to Henoch Schoenlein purpura (HSPIgAN) present with common histological features but different clinical outcomes, ranging from frequent remissions in HSPIgAN to progressive course in pIgAN. In both diseases a dysregulation of innate immunity is thought to result in failure of mucosal antigen elimination and/or altered IgA synthesis as well as inflammation. Innate immunity, particularly toll-like receptors (TLR), can modulate regulatory T (Treg) cells, which are crucial in downregulation of the immune response after infection and in autoimmunity. We previously reported increased TLR expression in peripheral mononuclear cells (PBMC) of patients with pIgAN.

Methods: We investigated a possible relationship between TLR expression in PBMC and Treg in children with pIgAN and HSPIgAN.

We studied 13 children with pIgAN (10 males, 3 females; mean age 10.71 +/− 3.90 years) and 21 children with HSPIgAN (12 males and 9 females; mean age 7.95 +/− 2.33 years; 10 with urinary signs, 11 without renal involvement).

TRL 2, 4 and 9 expression was detected by cell sorter analysis (FACS), as mean fluorescence intensity (MIF) and correspondent mRNAs quantification was performed by real time PCR (Taqman), normalizing values with Abelson murine leukaemia viral oncogene homologue 1 (Abl). Taqman was also used to measure mRNA expression of Foxp3 and TGF in PBMC.

Results: We observed a significant inverse correlation between TLR4 and Foxp3 mRNAs in PBMC of patients with pIgAN (r: −0.35, p < 0.05), while in cases of HSPIgAN TLR4 and Foxp3 mRNAs were directly correlated (r: 0.46, p < 0.05).

Conclusions: These data may suggest that in primary IgAN TLR4 hyperexpression and dowregulation of suppressors Tregs might turn into a proinflammatory and chronic outcome, while an enhanced Treg effect in front of a similar innate immunity engagement may favor the recovery commonly observed in children with HSPIgAN.

PS1-THU-135

Hypersensitivity vasculitis with acute nephritic syndrome in a 13 years-old girl as a result of co-infection

E. Kostadinova* ¹, V. Tzaneva¹, H. Djeneva¹

¹University Hospital, Medical Faculty, Thracian University, Stara Zagora, Bulgaria

Objectives and study: Many pathogenic microorganisms can induce a complex series of immunologic, endothelial-cell and cascades activation and dysfunctions.

Methods: We report the case of 13 years-old girl with hypersensitivity vasculitis, which developed during the course of a mixed infection with beta-hemolytic streptococcus and EBV infection. A month prior to hospitalization the girl had two episodes of purulent tonsillitis for which she received antibiotic treatment. After a week period without complains she is presented again with high temperature, chills, photophobia, insomnia, muscle pains, maculopapular rash and suppurative tonsillitis. In the next days haemorrhagic macules, papules and patches appeared on the face, neck, legs, billateral conjunctival ecchymosis, epistaxis and tonsillar hemorrhage. The medical condition manifests with deteriorated condition of the child, septic fever, generalized lymphadenopathy and hepatosplenomegaly. The clinical presentation is enriched with arterial hypertension up to 160/110 mm Hg,circulatory congestion, macroscopic haematuria,oliguria and acure renal failure in the context of acute nephritic syndrome. There is a history for several tick bites and a contact with dogs, without clinical evidence for Erythema migrans.

Results: After a wide range of differential diagnoses were discussed, the diagnosis: hypersensitivity vasculitis with acute nephritic syndrome was based on the clinical presentation and extensive screening of haematological, serological, microbiological and immunological tests. The ethio-pathogenic role of the preceding streptococcal infection and active EBV infection was verified. The history for several tick bites and positive enzyme-linked immunoassay (ELISA) for Borrelia Burgdorferi, detected in the active phase of the disease, required additional diagnostic procedures to clarify its role in the whole clinical presentation. As a result of the conducted treatment the pathological syndromes withdrew after two weeks, on discharge from the hospital the only pathologic finding was the microhaematuria. During the follow—ups in the next twelve months abnormalities were not registered.

Conclusions: This case is a demonstration of a severe clinical course as a result of the identified co-infection due to the development of complicated immunologic mechanisms. The positive serology for B. Burgdorferi without the presentation of the specific symptoms of Lyme disease is due to cross reaction.

PS1-THU-136

The hidden message of peritoneal dialysis effluent in paediatric patients

M. Bruschi¹, G. Candiano², L. Santucci¹, E. Giardina², G. M. Ghiggeri², E. Verrina* ²

¹RenalChild’s Foundation, c/o G. Gaslini Children’s Hospital, Genoa, Italy, ²Nephrology and Dialysis Unit and Laboratory on Physiopathology of Uremia, G. Gaslini Children’s Hospital, Genoa, Italy

Peritoneal dialysis effluent (PDE) is an attractive biochemical window into the peritoneum. It consists of a mixture of salts, sugars, lipids and proteins. Albumin, serotransferrin, a1-antitrypsin, a1-microglobulin and immunoglobulins are the predominant proteins in PDE, representing more than 60% of total protein amount. The abundance of these proteins limits the ability to identify potential biomarkers of peritoneal function or damage, which may have a lower concentration in PDE. In this study, combinatorial hexapeptide ligand library (ProteoMiner) was used to enrich low abundance proteins and simultaneously reduce the highly abundant proteins. The ProteoMiner elutions of PDE (PM-PDE) obtained from paediatric patients were compared by two-dimensional electrophoresis.

We studied 7 patients with median age of 3.9 years (range 0.3–11.7), body weight of 12.7 kg (2.79–35.3), body height of 90 cm (48–140.5), and body surface area of 0.55 m2 (0.18–1.12). Patients’ primary renal disease was renal dysplasia in 4 cases, nephronophthisis, hemolytic uremic syndrome and polycystic kidneys in 1 case each. At the moment of the study, patients had been on automated peritoneal dialysis (APD) with glucose-based solutions for a median of 19 months (range 2.5–38 months).

Image gel analysis revealed more than 1700 spots in the PM-PDE and about 1000 spots in the PDE. Therefore, combined proteomic approach highlighted a mean of 700 new proteins in each gel. Some differences in PDE proteome profile was observed in relation with duration of APD treatment. In particular, a greater amount of high molecular weight (100 kDa) proteins migrating in the basic region was found in patients on APD for more than 18 months.

The further step of our study will consist in the identification of isolated proteins by means of mass spectrometry , in order to clarify the biological meaning of the observed differences.

PS1-THU-137

Parental quality of life after pediatric kidney transplantation

A. Haavisto¹, C. Holmberg* ², H. Jalanko², E. Qvist²

¹Institute of Behavioural sciences, University of Helsinki, Finland, ²Pediatric Nephrology and Transplantation, Children’s Hospital, University of Helsinki, Finland

Treatment of chronic kidney failure, and subsequent kidney transplantation (TX) is demanding. To what extent this will influence parental quality of life (QOL) is not known.

The study group consisted of 45 kidney TX recipients who were compared to a control group of 38 liver- and heart TX recipients. Health related QOL assessments were collected from mothers of 38 kidney TX recipients (response 84%) and 34 (89%) controls.

QOL of mothers was assessed with the generic adult 15D□ instrument (scale 0–1, for best). The groups were compared for factors that may influence the parental burden: the child’s age at TX, follow up time since TX, the child’s age at assessment, neurological sequelae and outcome on the Achenbach parental (CBCL), self (YRF)- and teachers’ (TRF) ratings of psychosocial adjustment (T score, the lower the better).

Mothers to kidney TX recipients had a mean QOL score of 0.94 vs. 0.95 for controls (p = ns). Mean age at TX was 3.8 vs. 5.0, follow up time 7.1 vs. 6.5, and age at assessment 11.7 vs. 11.9 years, for kidney recipients and controls, respectively (all p = ns).

The groups did not differ with respect to neurological sequelae (36% for kidney and 42% for controls, p = ns). Scores on the parental ratings were 52 vs. 54 (p = ns), self-ratings 52 vs. 53 (p = ns), and teachers’ ratings 52 vs. 57 (p = 0.008) for kidney recipients vs. controls, respectively.Mothers of children with a kidney TX did not have a poorer QOL than mothers of children with a heart or liver TX. The groups were comparable with respect to risk factors, except that teachers rated the kidney TX recipients to have less psychosocial problems than the control group.

PS1-THU-138

The effectiveness or the effectiveless of CYP3A4 polymorphism on calsineurin inhibitor drugs trough levels in pediatric kidney transplantations

E. Toroslu¹, B. Sozeri* ¹, S. Mir¹, A. Berdeli²

¹Ege University Faculty of Medicine, Department of Pediatric Nephrology, Izmir, Turkey, ²Ege University Faculty of Medicine, Department of Moleculer Genetic, Izmir, Turkey

The main goal of clinical therapeutic is to individualize drug therapy to optimize the balance between efficacy and drug-related toxicity. Calsineurin inhibitor drugs—tacrolimus(Tac) and Cyclosporin A(Cyc A)- are the fundamental immunsupressions for kidney transplantation with narrow therapeutic indices and significant inter- and intra individual variability in blood concentrations under a fixed-dose regimen. These drugs are substrates of cytochrome P450 subgroup 3A (CYP3A) metabolic enzymes. CYP3A genetic polymorphisms may explain in part the variability observed in drug concentrations. The most frequent and important functional polymorphism consists of a 6986A⋄G transition within intron 3(CYP3A5*3), resulting in an aberrant mRNA and truncated CYP3A5 protein. The expression of CYP3A5 is significantly reduced in CYP3A5*3*3 carriers. We aim to determinate whether had an association CYP3A4 polymorphism genotype distribution, allele frequency with clinic impacts or not in patients who have been kidney transplant.

Log-transformed dose adjusted cyclosporine and tacrolimus trough concentration and daily dose per weight were compared 1, 3, 6, and 12 months after transplantation between CYP3A genotypes in 73 renal transplant recipients. We excluded the patients receiving medication that is interaction with Cyc A (diltiazem, nicardipine, verapamil, phenytoin, carbamazepine, fluconazole and ketoconazole). The main age was 12 ± 15 years. 34 were received Cyc A(Group I) , 39 patients were received Tac(Group II). We found that the frequency of CYP3A5*1 wildtype allele was 92% while the frequency of CYP3A5*3 allele was8% in our patients. CYP3A5*3 allele was determinate heterozygote in 5 patients in group 1. The cyclosporine trough concentrations were higher in these patients than others but not statistically significant. In group II, there were 6 patients carrying mutant allele (CYP3A5*3)in heterozygous.

In conclusion,mutant type genotype caused higher trough drug levels in all evolution times. However, we concluded individualized regimens should be requiered by genetic evaluations before therapy.

PS1-THU-141

Acute kidney injury in the pediatric intensive care unit: AKIN or pRIFLE criteria?

A. Kavaz¹, Z. B. Ozcakar¹, B. Bulum Ozturk¹, T. Kendirli², M. Ekim¹, F. Yalcinkaya* ¹

¹Ankara University, Medical School, Pediatric Nephrology, Ankara, Turkey, ²Ankara University Medical School, Pediatric Intensive Care, Ankara, Turkey

Background: Acute kidney injury (AKI) is an important clinical issue, especially in the critical care settings. However, there is a limited number of pediatric studies pertaining to AKI in critically ill patients. The aim of this study was to evaluate and analyze the prevelance and association of AKI as defined by pRIFLE and AKIN classifications.

Methods: An analysis of all patients admitted to our intensive care unit(with seven beds) between July 2009–July 2010 was performed. Patients were classified according to proposed staging system for AKI both by (pRIFLE and AKIN) classifications.

Results: One hundred eighty-nine patients (110 M;79 F-mean age 45.9 ± 54.7 months) were enrolled. Sixty-three patients (33.3%) developed AKI by AKIN. The stage of AKI according to the AKIN criteria was; 36.5% stage I, 20.6% stage II and 42.9% stage III. Sixty-eight patients (35.9%) developed AKI by pRIFLE. The patients classification according to the pRIFLE criteria was; 22.1% risk, 51.5% injury and 26.5% failure. Of the 63–68 patients, 64.7% had AKI on admision or within 24 h following admission to intensive care unit, 25% developed AKI within 2–7 days, and 10.3% developed ≥1 week after admission. 9 patients received RRT. Peritoneal dialysis was provided for 8 patients; continous venovenous hemodiafiltration fort he other patient. All of the 9 patients were classified as AKIN stage III at RRT initiation. Two of these patients were at stage I and seven were at stage F at RRT initiation. Overall mortality rate was 17.4%. The mortality rate was higher in patients who developed AKI than those who did not(33.3% vs. 9.4%).

Conclusion: Acute kidney injury developed in a significant number of pediatric ICU patients which was associated with a high mortality rate. Pediatric RIFLE criteria seems a little bit more sensitive in defining AKI in the pediatric ICU.

PS1-THU-142

Infectious complications in pediatric renal allograft recipients

A. Kavaz¹, B. Bulum Ozturk¹, Z. B. Ozcakar¹, E. Ince², M. Ekim¹, F. Yalcinkaya* ¹

¹Ankara University, Medical School, Pediatric Nephrology, Ankara, Turkey, ²Ankara University Medical School, Pediatric Infectious Diseases, Ankara, Turkey

Background: The aim of this study was to determine the incidence and outcome of infectious complications in pediatric renal allograft recipients.

Methods: Between March 2007 and December 2010, we evaluated the incidence of infections in 26 renal transplant patients (14 M;12F- mean age 169.1 ± 37.6 months). Four patients received cadaveric kidney transplantation, two received ABO incompatible kidney transplantation and one patient had intensive immunsupression. These patients considered high risk. Triple drug immunosupression with steroids, tacrolimus and mycophenolate mophetil were given to all patients in addition cadaveric renal transplantations received basiliximab and ABO incompatible patients received rituximab and plasmapheresis as induction therapies.

Results: The median duration of follow up of the patients was 17.7 ± 11 months (1,5–45). During the study period 83 infectious episodes in 26 patients with a mean of 3.3 ± 2.3 episodes (0–10). The mean time of the infection occurence was 242 ± 209 days (1–794) after transplantation. Sixty-three percent of the patients were hospitalized. In 7 high risk patients 38 infectious episodes occured whereas 45 infectious episodes were recorded in the other 19 patients. The most frequent infection was urinary tract infection(UTI) (29 infection episodes in 17 patients). Anatomical abnormalities and foreign materials such as double J catheters increase the risk of UTI. Ten episodes of CMV infection occured in seven patients. Two of three high risk patients with CMV infection had two episodes. Six patients showed an increase in creatinine during infection and two patients developed acute rejection after CMV infection. One patient (%3.8) died due to infection.

Conclusion: Kidney transplantation has made spectacular strides in the last few decades. These successes are largely due to more potent immunsupressive medications. However, infectious complications after renal transplantation are associated with significant morbididty and continue to be the most frequent cause of death. Clinician must be careful in this regard in the follow up.

PS1-THU-143

Hypertension in children after renal transplantation: diagnosis and follow-up

B. Bulum Ozturk¹, A. Kavaz¹, S. Altugan Cayci¹, Z. B. Ozcakar¹, E. Tutar², M. Ekim¹, F. Yalcinkaya* ¹

¹Ankara University, Medical School, Pediatric Nephrology, Ankara, Turkey, ²Ankara University Medical School, Pediatric Cardiology, Ankara, Turkey

Background: The aim of this study was to investigate frequency and clinical features of hypertension in children after renal transplantation.

Methods: Twenty four children (14 boys, 10 girls) who had had renal transplantation and followed-up at least six months after transplantation in our center between March 2007 and December 2010 were enrolled. Casual blood pressure (BP) measurements, ambulatory blood pressure monitoring (ABPM) and echocardiograms were performed at 1st week, 1st, 3rd, 6th month and then with an interval of 6 months after transplantation.

Results: The mean age at the time of the study was 14.2 ± 2.9 years and at the time of renal transplantation was 12.6 ± 3.0 years. The mean follow-up period was 18.1 ± 10.4 months. Hypertension was diagnosed in 46% of patients before and 88% after transplantation. Fifty-two percent of children who had hypertension after transplantation had also had hypertension before transplantation. The mean time of beginning of hypertension was 8.1 ± 9.9 days. Hypertension developed in 67% of patients within first week and 95% within first month. Casual mean BP’s were 151 ± 17/96 ± 10 mmHg at the first week and improved to 122 ± 14/76 ± 11 mmHg at the first month under treatments. While 78% of children had combined daytime and night-time hypertension, 22% had isolated night-time hypertension. No child had isolated daytime hypertension. At the last follow-up 43% of hypertensive children had controlled BP’s on antihypertensive therapy. The mean LVMI in hypertensive children before transplantation was 72.4 g/m2.7 and improved to 44.5 g/m2.7 after transplantation.

Conclusions: Severe hypertension was occured in the early period after renal transplantation. However, end-organ damage can be prevented with careful follow-up, early diagnosis and adequate antihypertensive therapy compared with the period prior to transplantation. In this situation, clinicians should be careful in terms of hypertension especially the first month after renal transplantation. As all patients had night-time hypertension, ABPM is required for diagnosis of hypertension in early post-transplantation period.

PS1-THU-146

Effects on ultrafiltration failure of mesenchymal stem cell transplantation in chronic peritoneal dialysis rat model

F. Baştuğ* ¹, Z. Gündüz¹, S. Tülpar¹, Y. Altuner Torun², H. Poyrazoğlu¹, R. Düşünsel², M. E. Dörterler³, İ. Dursun¹, O. Baştuğ⁴, S. Yel¹

¹Erciyes University Medical Faculty, Department of Pediatric Nephrology, Kayseri, Turkey, ²Kayseri Education and Research Hospital, Department of Pediatric Haematology, Kayseri, Turkey, ³Urfa Children Hospital, Department of Pediatric Surgery, Urfa, Turkey, ⁴Huma Obstetrics and Gynecology Hospital, Department of Pediatrics, Turkey

Backgraund: Ultrafiltration failure continues to be a major complication of peritoneal dialysis(PD), particularly long-term PD because of hyperosmolar and acidic PD fluids and episodes of peritonitis. The purpose of this study was to investigate whether the healing effect on ultrafiltration failure of mesenchymal stem cell(MSC) transplantation in chronic peritoneal dialysis rat model.

Methods: Sixty-eight male wistar-albino rats were divided into two groups. Study group (n = 60) received once-daily IP injection of 20 ml 3.86% glucose dialysis solution for 6 weeks and control group (n = 8) did not receive any injection and peritoneal permeability was evaluated by peritoneal equlibrium test (PET) at the end of 6 week period. Then, study group divided three groups. PDgroup (n = 8); PET was performed, MSCgroup (n = 26): MSC’s were administered IP injection dose of 1.5 million unit/kg and placebo(P) group (n = 26):placebo were injected equal amount with MSC at the end of 6 weeks. PET was performed to MSC and P groups at the end of first week(n = 8), second week(n = 9) and third week(n = 9), after receiving MSC and placebo.

Results: When compared with the control group, UF quantity significantly decreased in PD and P groups(P1-P2-P3) (P < 0.05) but no difference between control group and MSCgroups(MSC1-MSC2-MSC-3). Rate of glucose transport was high in PD, P-2 and P-3 PD, P-2 and P-3 groups was lower than control group(P < 0.05). However, in MSC-2 and MSC-3groups D/D0glucose was higher and D/PCr was lower than PD, P-2 and P-3 groups (P < 0.05).

Conclusion: PD group had high permeability UF failure. Our results showed that MSC transplantation has positive effects on ultrafiltration failure in chronic PD rat model. This is the first study, to our best information aimed to investigate effect on ultrafiltration failure of MSCs transplantation in chronic PD rat model. MSCs transplantation may be a hope for the renewal of the peritoneum in chronic PD patients with UF failure.

PS1-THU-147

End-stage renal disease in Slovak children: epidemiology from a European perspective

G. Kolvek* ^1,2, S. Reijneveld³, L. Podracka^1,2, J. Rosenberger^2,4,5,6,, I. Nagyova^2,7, R. Stewart³, J. van Dijk^2,3

¹1st Paediatric Department, Faculty of Medicine, P.J. Safarik University, Kosice, Slovak Republic, ²Graduate School Kosice Institute for Society and Health, P.J. Safarik University, Kosice, Slovak Republic, ³Department of Social Medicine, University Medical Center Groningen, University of Groningen, The Netherlands, ⁴Nephrology and Dialysis Center Fresenius, Kosice, Slovak Republic, ⁵Transplantation Department, Faculty Hospital L. Pasteur Kosice, Slovak Republic, ⁶1^st Internal Department, Faculty of Medicine, P.J. Safarik University, Kosice, Slovak Republic, ⁷Institute of Public Health—Department of Social Medicine, Faculty of Medicine, P.J. Safarik University, Kosice, Slovak Republic

Objectives and study: The aim of this study was to examine the occurrence of end-stage renal disease (ESRD) in Slovak children, to compare it with earlier Slovak data and with data from other European countries and to explore etiology.

Methods: Over the years 2003–2009 data on the incidence and prevalence of all cases of ESRD in children from all four Slovak tertiary pediatric centers were collected. The data were compared with two earlier Slovak studies and with European data from the European Society of Paediatric Nephrology.

Results: The median annual incidence rate of ESRD in Slovak children under 15 years of age was 6.6 per million age-related population (pmarp). The prevalence rate on 31st December 2009 was 24.1 pmarp. Compared with the last study (18.6 pmarp) the differences were not statistically significant. The comparison with neighboring countries and with the European average shows no significant difference in incidence, while prevalence is significantly lower compared to neighboring Austria, some other (mostly western) European countries as well as the European average. Etiology mainly concerned congenital anomalies (34.6%) and cystic diseases (19.2%).

Conclusions: During the past decade the incidence and prevalence rates of ESRD in Slovak children have remained stable. Compared to the European average the prevalence in Slovak children is significantly lower.

PS1-THU-157

The use of rituximab in paediatric renal transplant recipients

H. Jones* ¹, S. Patey¹, S. Marks¹

¹Great Ormond Street Hospital for Children NHS Trust, London, UK

Objectives: To review indication, treatment and outcomes with rituximab in paediatric renal transplant recipients (RTR).

Method: Retrospective analysis of all RTR receiving rituximab in a single renal transplant centre.

Results: 19 patients aged 5.7–17.5 (median 13.3) years(y) with 20 rituximab treatment episodes identified from 2002–11.

Five received rituximab at median 65 days with other treatments for post-transplant recurrence of focal and segmental glomerulosclerosis; three treated with a single dose of 750 mg/msq, one 2 doses and one given 4 weekly doses of 375 mg/msq. 60% responded (one with Stage V(T)-CKD, another requiring graft nephrectomy) with resolution of proteinuria and estimated glomerular filtration rates(eGFR) 20–76 mls/min/1.76 msq at 0.75–1.25 y post-transplantation. Six cases received rituximab for biopsy proven rejection with donor specific antibodies(DSA) at 0.04–12.5 (median 6.3)y post-transplant. Five patients have functioning grafts at 3.7–9.9 y from transplantation. Three patients received rituximab for rejection without DSA.

4 rituximab doses at 375 mg/msq were used to treat post-transplant lymphoproliferative disease (PTLD) in five cases presenting 0.5–7(median 0.8)y post-transplant. Two have resolution of disease at 0.8 and 1.3 y post diagnosis, one patient responded and transitioned to adult services. Two patients died; one had B-cell Burkitt phenotype non-Hodgkin\’s lymphoma receiving 2 doses rituximab before treatment withdrawn. The other had atypical HUS and developed PTLD 0.5 y post-transplant requiring chemotherapy but was unresponsive to therapy. One case of ABO incompatible transplant received rituximab (375 mg/msq) 4 weeks pre-transplantation. At 1.3 y follow up graft function is stable.

Conclusions: Rituximab has been used for a variety of indications in paediatric RTR. Further analyses needed to determine its benefits.

PS1-THU-161

Continuous renal replacement therapy in small neonates weighing less than 3 kg

H. S. Hyun* ¹, Y. B. Sohn¹, S. J. Kim², S. W. Park¹, S. Y. Cho¹, E. S. Kim¹, Y. S. Chang¹, W. S. Park¹, D. K. Jin¹, K. H. Paik¹

¹Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, ²Department of Pediatrics,Center for Pediatric Oncology, National Cancer Center, Goyang, Korea

Continuous Renal Replacement Therapy (CRRT) is becoming the treatment of choice for the support of critically ill pediatric patients. However, there are few studies reporting on CRRT use and outcome in small neonates. Here, the clinical application, complications and outcome of CRRT in eight neonates weighing less than 3 kg is reported by retrospective review of medical records. At the start of CRRT, the median age was five days (corrected age 38 + 2 weeks—23 days), and the median body weight was 2.73 kg (2.6–2.98). Sixty two patient-days of therapy were reviewed; the median time for CRRT was 7.8 days/patient (1–37 days). Adverse events on CRRT were electrolyte disturbances, catheter related complications and hypotension on connection with the CRRT. The mean circuit functional survival was 13.9 ± 8.6 hours. Overall, four (50%) patients survived; all four patients with multiorgan dysfunction syndrome (MODS) died.

In conclusion, complications in newborns on CRRT are relatively high. However, the results of this study suggest that venovenous CRRT is feasible and effective in small neonates weighing less than 3 kg under elaborate supportive care. Furthermore, to take advantage of the potential benefit of the CRRT in neonates, effort to prolong filter survival is needed.

PS1-THU-170

Novel mutations in patients with alport syndrome

J. Hoefele* ¹, S. Weber², S. Rath¹, I. Rost¹, H. G. Klein¹

¹Center for Human Genetics and Laboratory Medicine Dr. Klein and Dr. Rost, Martinsried, Germany, ²Pediatric Nephrology, University Children’s Hospital, Essen, Germany

Alport syndrome (AS) is characterized by ultrastructural abnormalities of the glomerular basement membrane with progression to end-stage renal disease, eye abnormalities and high-tone sensorineural deafness. Mutations in COL4A3 and COL4A4 can be associated with autosomal recessive or dominant AS, whereas mutations in COL4A5 cause X-linked AS. The X-linked form predominantly affects male individuals, female patients mostly have mild symptoms. In contrast to AS, the autosomal dominant inherited thin basement membrane nephropathy (TBMN) is characterized by persistent glomerular hematuria, minimal proteinuria and normal renal function. Mutations have been identified in COL4A3 and COL4A4.

In order to detect the relative frequency of novel mutations in our study population we examined 29 AS families and 2 TBMN families collected over 1 year. All AS patients were tested for mutations/deletions in COL4A5, COL4A4, and/or COL4A3 dependent on the family history. The TBMN patients were screened for mutations in COL4A3 and COL4A4.

In a large proportion of the investigated families novel mutations could be found (19/31 families; 61%). Altogether, we have detected 27 mutations in 25 different families: Seven COL4A3 mutations in 4 AS families and in one TBMN family (26%), three COL4A4 mutations in two AS and one TBMN family (15%), and 17 COL4A5 mutation/deletions in 17 AS families (63%). In six families no mutation was found (19%). 16/25 families had glycine mutations (64%). A high detection rate of 81% was achieved. 41% of patients with X-linked AS were female (7/17 patients), 10/25 of all patients with mutations were female (40%).

We have identified in most patients relevant mutations for AS and could detect a high number of novel mutations. The increased number of known mutations will facilitate future studies into genotype-phenotype correlations. The frequency of female patients with X-linked AS in our cohort is higher as described in the literature.

PS1-THU-174

Acute appendicitis in a patient on peritoneal dialysis (PD) with subsequent PD continuation

K. Zachwieja* ¹, M. Miklaszewska¹, D. Drożdż¹, M. Dizerżęga², B. Bogusz², A. Banach³, J. Pietrzyk¹

¹University Children’s Hospital JUMC, Department Of Pediatric Nephrology, Crakow, Poland, ²University Children’s Hospital JUMC, Department of Pediatric Surgery, Crakow, Poland, ³University Children’s Hospital JUMC, Department Of Pediatric Radiology, Crakow, Poland

Appendicitis is a rare cause of acute abdomen in children on PD and may cause diagnostic difficulties. Patient S.W. 11 years of age, with VUP as a cause of renal failure, and Silver-Russell syndrome treated with PD for 13 months, was admitted because of vomiting and severe abdominal pain. On physical exam the pain and tenderness in right lower region of the abdomen with muscle guarding were found. The severity of symptoms showed variability (doubts in the subsequent surgical opinions). By ultrasound—the structure of tubular hypoechogenic mass on the right lower region of the abdomen was seen. On admission, dialysis fluid was clear and transparent, fluid cytosis: 86, the fluid culture was negative initially! Blood test revealed: WBC −16 700, low CRP value. This clinical picture was not typical for the PD related peritonitis. Despite the start of empiric intraperitoneal treatment, the worsening of the clinical picture was observed. The severity of pain increased and cloudy dialysis fluid appeared (fluid cytosis after 48 hours—51 000!) The serum CRP increased. After 2 days the patient underwent appendectomy which confirmed gangrenous perforated retrocecal appendicitis. The fluid culture tested on day of the appendectomy was positive for E. coli and Bacteroides fragilis. After the laparotomy one HD session was necessary. The cloudy dialysis fluid was observed for following week. The antibiotic therapy lasted for 3 weeks. The peritoneal dialysis has been continued, either.

Conclusions: 1. Occurrence of severe symptoms of acute abdomen in a patient on PD without typical symptoms of PD related peritonitis and lack of response to empiric treatment indicates the need of the surgery. 2. The presence of dialysis fluid can significantly change the results of surgical evaluation, however it should be repeated after dialysate outflow.

PS1-THU-175

The role of soluble Fas/FasL and matrix metalloproteinases in apoptosis regulation in children and young adults on chronic dialysis

K. Musial* ¹, D. Zwolinska¹

¹Wroclaw Medical University, Department of Pediatric Nephrology, Wroclaw, Poland

Objectives and study: The system of membrane receptor Fas and its ligand FasL compose one of the main pathways triggering apoptosis. However, the role of their soluble forms has not been clarified yet. Although sFasL can be converted from the membrane-bound form by matrix metalloproteinases (MMPs), there are no data on relations between sFas/sFasL, MMPs and their tissue inhibitors (TIMPs) in patients on chronic dialysis—neither children nor adults. Our aim was to evaluate serum concentrations of sFas, sFasL, and their potential regulators (MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-2), in children and young adults chronically dialyzed.

Methods: 22 children on automated peritoneal dialysis (APD), 19 patients on hemodialysis (HD) and 30 controls were examined. Serum concentrations of sFas, sFasL, MMPs and TIMPs were assessed by ELISA.

Results: Median values of sFas, sFasL, sFas/sFasL ratio, MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 were significantly elevated in all dialyzed patients vs. controls, the highest values being observed in subjects on HD. A single HD session caused the decrease in values of all parameters to the levels below those seen in children on APD. Regression analysis revealed that MMP-7 and TIMP-1 were the best predictors of sFas and sFasL concentrations.

Conclusions: Children and young adults on chronic dialysis are prone to sFas/sFasL system dysfunction, more pronounced in patients on hemodialysis. The correlations between sFas/sFasL and examined enzymes suggest that MMPs and TIMPs take part in the regulation of cell death in the pediatric population on chronic dialysis, triggering both anti- (sFas) and pro-apoptotic (sFasL) mechanisms.

PS1-THU-178

Glycogen synthase kinase-3β and inadequate heat shock response after incubation with low PH peritoneal dialysis fluids

K. Rusai* ¹, R. Herzog¹, L. Kuster¹, B. Bidmon¹, K. Kratochwill¹, C. Aufticht¹

¹Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria

Peritoneal dialysis (PD) causes injury of mesothelial cells leading to fibrosis and decline of ultrafiltration capacity of the peritoneal membrane. Heat-shock proteins (HSPs) protect cells from injury and their level is usually elevated under stress conditions as part of the cytoprotective heat shock response (HSR). Recent studies suggest that long-term exposure to PD fluid (PDF) induces only an inadequate elevation in HSP levels disabling mesothelial cells to cope with stress that results from dialysis. However, the cause and background mechanisms are not known. Met5a mesothelial cells were exposed to PD4 Dianeal 3.86% dialysis fluid (pH 5.8) for up to 2 hours. Cell death, heat shock factor-1 (HSF-1) activation and HSP-72 production of cells were analyzed at different recovery times.

Exposure of mesothelial cells to PDF caused high cell death rate with high lactate dehydrogenase (LDH) release indicating severe cellular stress, but resulted only in a low HSP-72 production confirming an inadequate HSR. This was paralleled by blunted HSF-1 activation demonstrated by absent nuclear shift, hyperphosphorylation and heat shock element (HSE) binding. Activation of the HSF-1 inhibitor glycogen synthase kinase-3β (GSK-3β) was significantly higher in PDF treated cells compared to controls. When pH of the PDF was normalized, there was a significantly lower GSK-3β activation associated with an upregulation in HSF-1 nuclear shift, hyperphosphorylation and HSE binding leading to significantly higher HSP-72 expression and lower cell death rate with lower LDH release.Our results clearly indicate that inadequate HSR after PDF incubation is mediated at the GSK-3β - HSF-1 level. Furthermore, low pH level of PDF might be responsible for the inadequate HSR induction through activation of the HSF-1 inhibitor GSK-3β. Future studies are needed to evaluate the exact molecular mechanism and to demonstrate its biological role in in-vivo models of PD.

PS1-THU-179

Urine neutrophil gelatinase—associated lipocalin (NGAL) as a marker of acute kidney injury (AKI) in children

K. Blahova* ¹, F. Fencl¹, V. Stara¹, M. Pechova², R. Prusa²

¹Department of Paediatrics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic, ²Department of Clinical Biochemistry and Pathobiochemistry, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic

Objectives: Acute kidney injury (AKI) is a frequent and serious condition. Clinically it is most important to diagnose it at an early stage. Urine neutrophil gelatinase-associated lipocalin—a 25 kDa protein—(NGAL) levels rise steeply immediately after kidney injury (2 hours after serious ischemic insult). Urine NGAL seems to be a promising biomarker (“renal troponin”) of AKI.

Materials: Urine samples from 14 pts with AKI (ischemic injury, tubular necrosis), 10 pts with chronic kidney diseases (CKD- nephrotic syndrome, IgA nephropathy), 3 pts with prerenal azotemia and 10 healthy controls were obtained.

Method: Serial of 37 urine samples were analysed by ARCHITECT Urine NGAL assay/analyzer—a chemiluminiscent microparticle immunoassay (CMIA) for rapid quantitative detection of NGAL. The defined normal urine NGAL was ≤131.7 ng/mL. Statistical analysis was performed using GraphPad Prism.

Results: Urinary NGAL levels in pts with AKI (median: 1 700 ng/mL, maximal levels: >6 000 ng/mL) were significantly higher (p < 0.0001, p < 0.0001) than in controls (median: 7.1 ng/mL, maximal level: 51 ng/mL) and pts with CKD (median: 9.7 ng/mL, maximal level: 99.4 ng/mL). 200-fold higher difference in the median values of pts with AKI compared with controls and pts with CKD were detected. Statistical analysis of pts with prerenal azotemia (small number of pts) was not performed (maximal level: 56.0 ng/mL). The courses of urinary NGAL levels of 3 pts with AKI during 3 weeks are demonstrated.

Conclusion: Urinary NGAL may be useful for the diagnosis, treatment (optimize hemodynamics after cardiac surgery, monitoring after renal transplantation, avoid nephrotoxic medication) and for the prediction of clinical outcome.

It is to be expected that serial rather than isolated single measurement of urinary NGAL will provide the most useful data.

PS1-THU-184

Living kidney donation to paediatric receptors: a satisfaction survey

M. Navarro* ¹, J. G. Caballero², P. Aparicio¹, M. Melgosa¹, M. P. González¹, L. Espinosa¹

¹Nefrología Infantil. Hospital Universitario Infantil La Paz, Paeditaric Nephrology Unit, Madrid, Spain, ²Nefrología Infantil. Hospital Universitario Infantil La Paz, Preventive Medicine Unit, Madrid, Spain

Methods: Since 1994, we have performed 75 living donor kidney transplants. We conducted a telephone survey with 26 questions covering information about the process, medical care and attention before and after transplant. Donors were: mothers, 69.4%, and fathers, 30.6%. The average donor age was 40.3 + 6.9 years (27–54 years) and the average receptor age was 10.5 + 5.5 years (1.9–23.8 years).

Results: Responders expressed dissatisfaction with the information about the process of the transplantation (2.8%), risks for the donor (5.6%), the pretransplant tests information (8.3%) and the unexpected length of the waiting period (34.7%). Care provided by the different services was evaluated on a scale from 1 (very bad) to 10 (very good). The following Services received a score of 8 or better from a given percentage of responding parents: Adult Nephrology (73.6%) , Urology (76.5%), Ethics Committee (78.2%) and Transplant Coordination Unit (90.2%). 33.3% of the laparoscopic donors considered the evolution of surgery to be worse than expected compared to 24.4% of open surgery donors. Pain was worse the expected in 48% of the donors and 30.6% were dissatisfied with the length of hospital stay. Post-donation follow-up was deemed appropriate by 75.7% of the donors, who thought the receptor’s follow-up was appropriate in 95.8% of the cases. 84.7% of the donors are not worried about their health after donation, 88.9% reported successful integration into working life and 98.6% expressed satisfaction with the kidney donation.

Conclusions: Living donor kidney donation in paediatric centres entails different services for donors and receptors. This study, in spite of the bias probably resulting from the passage of time and the results of the transplantation, shows general satisfaction with the process although some aspects of our communication with potential donors can be improved.

PS1-THU-185

Urological and vascular complications after kidney transplantation in children: Spanish multicenter study

L. Espinosa* ¹, C. Fdez Camblor¹, L. E. Lara², M. J. Sanahuja³, G. Ariceta⁴, F. De la Cerda⁵, A. Vila⁶, M. N. Plana⁷, A. E. González⁷ Spanish Group of Surgical Complications in Paediatric Kidney Transplantation

¹Hospital La Paz, Madrid, Spain, ²Hospital Vall de Hebrón, Barcelona, Spain, ³Hospital La Fe, Valencia, Spain, ⁴Hospital de Cruces, Bilbao, Spain, ⁵Hospital Virgen del Rocío, Sevilla, Spain ⁶Hospital San Joan de Deu, Barcelona, Spain, ⁷Clinical Biostatistics Unit. H. Ramón y Cajal, Madrid, Spain

Purpose: To estimate the incidence of urological and vascular complications after kidney transplantation (KT) in children during the first year post intervention and to explore associated risk factors.

Method: Medical records of all pediatric kidney transplants performed between 2004 and 2007 in six Spanish hospitals were reviewed. Donors and recipients demographics and clinical data were collected as well as data of the grafting surgical procedure.

Results: 220 patients younger than 18 years of age received a transplant: 87.6%, from a deceased donor, 20.1% of the patients have had a previous kidney graft and 95% were isolated KT. 57.8% of the recipients were males with a median age of 11 years (IQR 5.3–14.6). Most of the recipients were on dialysis (71.4%), for an average of 7.8 months (SD 12.2). The cumulative incidence of urological complications was 10.5% being the most frequent complication urinary stenosis/obstruction. Vascular graft complications were observed in 23 patients (10.5%), and thrombosis was the most frequent. Graft lost occurred in 23 patients (10.5%) and one patient died. Vascular graft thrombosis was present in 75% of these 24 patients. Among several factors analyzed, recipient’s age was consistently associated with the risk of complication. Older recipients were more likely to have urologic complications (p = 0.005). Older recipients were more likely to have urologic complications, while the younger recipients were more likely to suffer vascular complications. Consequently weight and height were also associated with the risk of complication. However, obesity (Body Mass Index >97 percentile) was not associated with poor outcome.

Conclusión: Urological and vascular complications in children are frequent after KT and adequate preventive measures are needed, particularly to prevent vascular problems.

PS1-THU-186

Paediatric kidney transplantation in a Spanish center: experience of 25 years

L. Espinosa* ¹, C. García Meseguer¹, A. Alonso¹, C. Fernández¹, M. Melgosa¹, A. Peña¹, J. Bravo¹, M. J. Martinez Urrutia², E. Jaureguizar², M. Navarro¹

¹Nefrología Infantil. Hospital Universitario Infantil La Paz, Paeditaric Nephrology Unit, Madrid, Spain, ² Nefrología Infantil. Hospital Universitario Infantil La Paz, Paediatric Urology Unit, Madrid, Spain

Objectives: We report our experience with renal transplantation in paediatric receptors. Methods: From 1985 to 2010, 345 kidney transplantations were performed (219 male and 126 female), 81 from living donors (LKT), 264 from deceased donors (DKT). Simultaneous liver and kidney transplantation were performanced in 9 cases. The standard immunosuppressive protocol is: triple therapy with steroids, mycophenolate mofetil/azathioprine and cyclosporine/tacrolimus and from 1991 with induction (baxilisimab/thymoglobuline).

Results: Aetiology of ESRD: Obstructive uropathy/displasia/hipoplasia/reflux nephropathy 171 (59%), hereditary 91 (96%) and glomerular 37 (11%). Mean age 10.4 ± 5.2 years. Pre-emptive transplantation was done in 24.3% (48% LKT and 17% DKT) .8 receptors died (4 due to infection, 2 cardiovascular diseases, 1 leukemia and 1 during liver retransplantation). The actuarial patient survival is 97.9%, 97.5% and 96.8% at 1, 5 and 10 years and the graft survival is 90.1%, 76.6% and 58.4% respectively. Comparing by decades, the graft survivals at 1 and 5 years are 81.5% and 59.3% in the 1980s, 86.8% and 75.7% in the 1990s and 96% and 84.3% since 2000. Since we started living donor programme in 1994, graft survival at years 1, 5 and 7 is 97.5%, 86.5% and 82.9% for LKT vs. 91.3%, 81% and 74.1% for DKT. A total of 108 grafts failure have occurred, the most common causes are immunologic (69.4%), thrombosis (3.7%) and recurrence of original disease (9.3%). The available information on rejection episodes (in 241 grafts) since 1994 shows that 28.2% had at least one rejection episode (32.3% of DKT vs. 20% of LKT).

Conclusions: Graft survival at 5 years has improved by 25% in the last 20 years. Live Kidney transplantation in children is the best treatment for ESRD with an 8.8% improvement in graft survival at 7 years in relation with DKT, the receptors with LKT have the lowest incidence of rejection.

PS1-THU-189

Safety and efficacy of everolimus and low dose cyclosporine in pediatric kidney transplantation

M. Belingheri¹, L. Murer², F. Ginevri³, L. Dello Strologo⁴, M. Ferraresso⁵, E. Groppali¹,G. Ghirardo², A. Parodi³, I. Guzzo⁴, L. Ghio*¹

¹Pediatric Nephrology Unit, Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico, Milan, Italy, ²Pediatric Nephrology, Dialysis and Transplant Unit, Az Ospedaliera-University of Padova, Padova, Italy, ³Clinical and Experimental Medicine of Organ Transplantation, IRCCS Gaslini Institute, Genova, Italy, ⁴Nephrology and Urology Department, Bambino Gesù Children’s Research Hospital, Rome, Italy, ⁵Dept. Surgical Science, University of Milan Medical School, Milan, Italy

Introduction: The aim of this study was to assess the safety and the efficacy of a low-dose Cyclosporine(CYA)-Everolimus(EVE) combination in pediatric kidney transplant recipients (kTx).

Materials and methods: From 2008 to 2010 we enrolled 41 pediatric patients from 5 different pediatric programs. Mean age of the recipients was 9.15.4 yrs. Immunosuppressive regimen included: CYA (10 mg/kg/die) and MMF(600 mg/m2 BID) from POD#1 and delay introduction of EVE on POD#21 (0.8 mg/m2 BID, adjusted to a trough level 5–10 ng/ml.) with simultaneous discontinuation of MMF and 50% reduction of CYA initial dose. CYA dose was targeted to a 2nd hour post-dose concentration of 500–700 ng/ml (#21-#60 POD), 400–600 ng/ml (#61-#90POD) and 200–400 (>#61POD). Blood pressure values, sCreatinine, sCholesterol, sTriglyceride, PCR-CMV, PCR-EBV,PCR-BKV and uProtein were recorded 7, 14, 28, 90, 180, 270 and 360 POD as well as any immunological and non immunological adverse events. Protocol kidney biopsies were obtained on POD#180 and #360.

Results: Four patients were dropped before EVE administration because of hypercholesterolemia, surgical complication, chronic low platelet count and exitus. One year patients\’ and graft\’s survivals after EVE introduction were 100%. We experienced 18% of acute rejection, 5% of subclinical rejection and 6% of chronic allograft nephropathy. Any adverse event was recorded. Renal function, blood pressure values, lipid profile and virus infections were not impaired by EVE introduction and were comparable with our historical controls. After 1 year of follow up only 9% of patients showed histological patterns of CNI toxicity.

Conclusions: Low- dose CYA and EVE provide a safe and effective immunosuppression in pediatric kidney transplant recipients and seems to reduce CNI toxicity.

PS1-THU-190

Involvement of nuclear receptor SXR SNPS in cyclosporine pharmacokinetics variability during the first year post kidney transplantation

M. Belingheri¹, M. Ferraresso², E. Groppali¹, S. Turolo¹, S. A. Tirelli³, P. Grillo⁴, A. Edefonti¹, L. Ghio*¹

¹Nephrology and Dialysis Unit, Fondazione IRCCS Ca’ Granda, Maggiore Hospital Policlinico, Milan, Italy, ²Dept. Surgical Science, University of Milan Medical School, Milan, Italy, ³Laboratory of Clinical Pathology, Fondazione IRCCS Ca’ Granda, Maggiore Hospital Policlinico, Milan, Italy , ⁴Epidemiology Unit, Department of Occupational and Environmental Health, Fondazione IRCCS Ca’ Granda, Maggiore Hospital Policlinico, Milan, Italy

Introduction: In this study we investigated the relationships between CyA exposure and CyP3A5, MDR1 and the steroid X receptor (SXR) SNPs, to rule out any possible pharmacokinetics effect on CyA profile during the first year after kidney transplantation (kTx).

Materials and methods: The study involved 65 pediatric kidney transplant recipients (32 females and 33 males, mean age 13.26 6.2 years). All the patients were genotyped for CYP3A5, MDR1 (C3435T, C1236T, G2677T and IVS21 + 49) and SXR (−200GAGAAG/- and A7635G) SNPs. CYA trough level (C0), weight normalized CyA dose (nDose) and normalized C0 (C0/nDose) were recorded at 30, 90, 180 and 360 days after kTx and compared between different genotypes.

Results: ANOVA test for repeated measures corrected for age, rejection episodes and steroid doses, didn\’t show any significant difference in nDose, C0 and nC0 for CYP3A5 and MDR1 polymorphisms. In patients with homozygous deletion of 6 bp in SXR gene, a significantly lower CyA nDose and nC0 was observed when compared to heterozygous or wild groups (p < 0.05).

Discussion and conclusion: According to our observation SXR represents the only polymorphism affecting CyA metabolism. Since SXR is a central regulatory mechanism of CYP3A enzymes and transport proteins like the permeability-glycoprotein, the high inter and intra-individual variability of CYA levels could be potentially related to its genetic polymorphism.

PS1-THU-197

Analysis of growth and weight disorder in children with stage 2–5 chronic kidney disease in Russian federation

M. Molchanova* ¹, S. Kazymova¹, E. Molchanova², E. Petrosyan¹

¹Russian State Medical University, Moscow, Russia, ²Russian Children’s Clinical Hospital, Moscow, Russia

Objectives: Growth and weight disorder is one of the most important signs of chronic kidney disease (CKD) in children. It is considered as a social problem affecting children adaptation and at the same time a medical problem worsening disease prognosis and complicating kidney transplantation. The goal of the research was to investigate growth and weight delay in children with stage 2–5 CKD.

Methods: We examined data of 960 children with stage 2–5 CKD contained in Russian CKD Pediatric Database of the year 2008; age 12.8 ± 4.2 (range 1–17.9) years. Among them 834 children (519 boys, 315 girls) with stage 2–4 CKD and 126 (69 boys, 57 girls) with stage 5 CKD undergoing dialysis. Children height and weight were assessed using centile tables.

Results: The analysis revealed that in the group of children with stage 2–4 CKD height of 36.99% patients and weight of 32.26% were below 5 centile. In the group of dialysis patients height of 57.94% and weight of 63.49% were below 5 centile. Patients with cystic renal dysplasia, renal hypoplasia, obstructive uropathy, oncology diseases and tubulopathy showed the most significant growth and weight delay (p < 0.05). The research revealed that growth and weight disorder in dialysis patients increased with dialysis duration (p < 0.05) and growth disorder increased with disease duration (p = 0.003). No significant correlations were found between weight delay and disease duration in both groups.

Conclusions: We concluded that there is severe growth and weight delay in children with CKD in Russia. It depends on disease and dialysis duration as well as on diagnosis. Its early detection and proper treatment can lead to improvement of clinical conditions.

PS1-THU-198

The long-term effect of rhGH on final height and bone health in renal transplant patients

M. Van Dyck* ¹, J. Herman¹, N. Knops¹, R. Van Damme-Lombaerts¹

¹University Hospitals Leuven, Department of Pediatric Nephrology, Leuven, Belgium

Objectives and study: The long-term effect of rhGH on final height(FH) and bone health in renal transplant patients was studied.

Methods: 21 patients, born between 1985 and 1994, were studied. 15 patients (12 boys) received rhGH during 3.0 yrs before transplantation (group A). Of those 3 boys required rhGH again for 3.5 yrs after renal graft. 6 patients received no rhGH before transplantation, 3 of them (girls) required rhGH after transplantation for 4 yrs (group B). The two groups were not different for median age at transplantation, median follow-up period after transplantation and median GFR at FH evaluation.

FH was expressed as SDS. Lumbar spine density(LBMD) and body composition were studied by DXA (Discovery A). LBMD was expressed as standardized lumbar bone density L2-L4(sLBMD) according to normative data of Belgian healthy young adults. Osteoporosis was defined as a sLBMD T-score of −2.5 SDS. Lean body mass was expressed as percentage of the total body weight.

Results: Median height SDS at transplantation was −0.3 in group A and −1.7 in group B (p = 0.03). FH SDS was comparable (−0.46 in group A versus 0.14 in group B, p = 0.6). BMI SDS was within the normal range. Lean body mass % was significantly higher in group A (80.7) compared to group B (72.6) (p = 0.02). LBMD was better at the moment of renal transplantation in group A, but no longer after reaching FH (−1.35 in group A versus −1.20 in group B, p = 0.146).

Conclusion: In children with chronic renal failure rhGH treatment improves height and results in better bone health at the moment of transplantation. At FH patients with rhGH before transplantation have significantly better lean body mass.

PS1-THU-203

Renal transplantation from a living donor in a child with donor specific antibodies (DSA)

E. Allain-Launay*¹, G. Karam¹, M. Hourmant¹, A. Cesbron², A. Devys³, G. Roussey-Kesler⁴

¹Department of Pediatric, Urology and Nephrology, University Hospital Nantes, France, ²Histocompatility Laboratory, Etablissement Français du Sang, Nantes, France, ³Histocompatility Laboratory, Etablissement Français du Sang, Nantes, France, ⁴Department of Pediatric, Urology and Nephrology, University Hospital Nantes, France

Case report: G, 12-year-old boy, received a first pre-emptive transplantation at eight years of age, with two class I mismatches and 1 DQ mismatch. A massive thrombosis led to graft loss and initiation of chronic hemodialysis. Immunosuppression was stopped within a few days. Subsequently major immunization, more than 86% in class I and II, appeared with an anti-A 24. All lymphocytotoxicity (LCT) familial cross matches were positive and poor probabilities for a second transplantation from a deceased donor were calculated. After four years in hemodialysis, we decided to initiate a new protocol of desensitization for a familial graft. Matching with his father was almost complete except for the A24 antigen. A decrease in anti-A24 levels (Mean Fluorescence Intensity from 13183 to 806) was obtained after nine plasmapheresis (PP) and intravenous immunoglobulins (IVIG). It was then decided upon to proceed with a transplant: Tacrolimus and Mycophenolate Mofetil were started two weeks before, nine PPs were inititated three weeks before, and IVIG the day before (2 g/kg). The LCT cross-match was negative, the flow cytometry cross-match became less positive and DSA were low (MFI 710). Immunosuppressive therapy was purchased with anti-lymphocyte serum, steroids, an injection of anti CD20 at day five, PP until week +3, and IVIG at week three, six and nine after transplantation. Graft function remains normal (serum creatinin at 90 μmol/L without proteinuria) and renal biopsies at one and three months post-transplantation are normal without C4d fixation. The level of DSA is negative.

Conclusion: This intra-familial transplantation with positive DSA was carried out with an intensive desensitization protocol. At three months, no sign of acute humoral rejection have been noted. Hyper-immunization is now a frequent problem in adult recipients, but managing it in pediatric patients is becoming more frequent. Only a few case reports concerning post-desensitization renal transplantation in children have been published and major studies are needed to assess the best strategies for these cases.

PS1-THU-204

Trimethoprim-sulfamethoxazole associated glomerulotubular zebra bodies

M. Torun Bayram*¹, Y. Öztürk¹, A. Soylu¹, M. Türkmen¹, S. Kavukçu¹

¹Dokuz Eylül University Department of Pediatrics, Division of Pediatric Nephrology, Izmir, Turkey

Introduction: Electron-dense multilamellar myelin figures (zebra bodies) may be seen in renal cells due to lipid accumulation in lysosomal storage diseases. Iatrogenic phospholipidosis associated with drugs like amiadaron, chloroquine, hydroxychloroquine and gentamycin has been reported to cause similar morphologic appearance in kidney. We present a case with asymptomatic proteinuria having renal zebra bodies probably related to trimethoprim-sulfamethoxazole (TMP-SMX).

Case report: 11-year-old girl with recurrent urinary tract infections (UTI) was referred for proteinuria. Radiologic evaluation for UTI was reported to be normal. Her parents were first degree relatives and her elder brother had end stage renal disease. Physical examination and laboratory tests were normal except postural proteinuria. We performed renal biopsy due to family history. Light and immunofluorescence microscopiy was normal, but electron microscopy revelaed glomerulotubular zebra bodies. α-galactosidase A level and genetic analysis of the patient and her brother for Fabry disease were normal. As her clinical and laboratory evaluation were not compatible with other lysosomal storage diseases, we considered her renal biopsy findings to be associated with TMP-SMX used for UTI prophylaxis for one year.

Discussion: A case of hepatic phospholipidosis associated with hepatocellular necrosis and cholestasis due to TMP-SMX has been reported in the literature. Hepatic lysosomal inclusions persisted for a few months despite plasmapheresis treatment. Pathogenesis was attributed to the lipophilic N1-acetylsufamethoxazole metabolite. Because of genetic polymorphism and substantial individual variations in the metabolism and acetylation of sulfa drugs, susceptible individuals may have an abnormal acetylator phenotype leading to increased formation of the lipid-soluble N1-acetyl metabolite and thereby resulting in cholestasis and phospholipidosis by injury to cell membranes and accumulation in lysosomes. Alternatively, phospholipidosis may result from inhibition of the lysosomal enzyme phospholipase A, by TMP-SMX. We would like to emphasize the possibility of a similar mechanism leading to renal lipidosis in our patient.

PS1-THU-205

Ocular complications in pediatric renal allograft recipients

C.S. Dogan¹, C. Apaydin², E. Comak¹, A. Uslu Gökceoglu¹, A.E. Kuybulu¹, M. Koyun* ¹, S. Akman¹

¹Akdeniz University Medical Faculty, Department of Pediatrics, Division of Pediatric Nephrology, Antalya, Turkey, ²Akdeniz University Medical Faculty, Department of Ophtalmology, Antalya, Turkey

Aim: The aim of this study was to analyze the frequency and risk factors of ocular complications in pediatric renal transplant recipients.

Methods: In children who had undergone renal transplantation at our hospital between August 1994 and December 2009, the patients with a normal ophthalmological examination prior to transplantation and with a follow-up period of at least 12 months post-transplant were included in the study. First ophthalmological examination was performed within 6 months post-transplant or prior to transplantation; then it was repeated annually.

Results: 70 children, 42 boys (60%), with a mean age of 14.3 ± 4.2 years and median follow-up period of 26.5 (12–123) months, were included. A total of 13 patients (18.5%) developed ocular complication within a median period of 15 (6–96) months. The most common complication was hypertensive retinopathy (HTRP) (n = 10, 14.2%), followed by posterior subcapsular cataract (n = 4, 5.7%) (2 patients had both); one patient had elevated intraocular pressure. Six of 10 children with HTRP had hypertension before the transplantation period. Six and four patients with HTRP had grade I and grade II HTRP, respectively. No statistically significant correlation was found between the occurrence of ocular complications and the age at transplantation, follow-up period, duration of time on dialysis, acute rejection episodes, previous corticosteroid therapy, donor source, glomerular filtration rate.

Conclusion: Pediatric renal allograft recipients should be screened periodically for ocular examination at the post-transplantation period to prevent significant ocular morbidity.

PS1-THU-211

Parvovirus B19 Infection in renal transplant recipient

A. Kavaz¹, M. Ekim*¹, B. Bulum Ozturk¹, S. Altugan Cayci¹, Z.B. Ozcakar¹, F. Yalcinkaya¹

¹Ankara University, School of Medicine, Pediatric Nephrology Department, Ankara, Turkey

Red cell aplasia due to parvovirus B19(PV B19) infection has been reported among patients receiving immunosuppressive drugs after organ transplantation. Here we report two renal transplant recipients with PV B19 infection presenting with a severe anemia.

Case 1: A 14 year-old boy, with polycystic kidney disease re¬ceived kidney graft from a cada¬veric donor. He was on triple immunosuppressive regimen (MMF, tacrolimus and prednisolone) for 13 months, with normal renal function. He was admitted to our clinic with the complaints of vomiting and pallor. On his physical examination, there was no pathological findings other than pallor. Laboratuary examinations showed normochromic, normocytic anemia (hemoglobin levels ranged from 6.1–8.4 g/dl). Reticulocytes percentage was 0%. Feritin and folat levels were normal. A search for PV B19 DNA by PCR in blood cells was positive.

Case 2: A 10-year-old girl, with nephronophthisis, received kidney graft from ABO mismatch mother. She had an uneventful transplantation course, and was on triple immunosuppressive regimen (MMF, tacrolimus and prednisolone). Acute rejection was developed in the tenth month of transplantation. She was admitted with complaints of pallor 13 month after tranplantation. There was no pathological findings other than pallor on her physical examination. Laboratuary examinations showed normochromic, normocytic anemia (hemoglobin levels ranged from 6.9–9.9 g/dl). Reticulocytes percentage was 0%. Feritin and folat levels were normal. A search for PV B19 DNA by PCR in blood cells was positive.

Both of patients received recevied blood transfusions, immunosupression reduction and IVIG theraphy was given. The hemoglobine levels in each patient improved at the first month after theraphy. In conclusion, PV B19 should be considered in the differantial diagnosis of persistent anemia in renal transplant recipients.

PS1-THU-215

Elimination of calcineurin inhibitors in paediatric renal transplant recipients

A. A. Prytula*¹, E. Dorresteijn¹, R. van Rooij¹, M.G. Keijzer-Veen¹, K. Cransberg¹

¹Department of Pediatric Nephrology, Erasmus Medical Center- Sophia Children’s Hospital, Rotterdam, The Netherlands

Objectives: There is a growing number of reports on the use of everolimus in paediatric renal transplant recipients with calcineurin inhibitor (CNI) intolerance or chronic allograft nephropathy. We report the outcome of this alternative immunosuppressive regimen at the Sophia Children’s Hospital in Rotterdam.

Methods: In 5 out of 41 renal transplant patients aged 7–14 years CNI were partially (n = 1) or fully (n = 4) replaced by everolimus 0.3 to 8.5 years following transplantation. Concomitant immunosuppression consisted of mycophenolate mofetil (n = 4), prednisolone (n = 2) and low dose cyclosporine A (n = 1). Indications included chronic fatigue and headache (n = 2), encapsulating peritoneal sclerosis (n = 1), intracranial hypertension with papillary oedema (n = 1) and chronic allograft nephropathy with refractory arterial hypertension (n = 1). The follow-up period was 4–8 months. The target everolimus trough level was 4–9 μg/l.

Results: The mean dose of everolimus was 1.5 mg/m²(range 1.2–2 mg/m²). The mean eGFR at everolimus commencement was 68 ml/min/1.73 m² (range 39–110 ml/min/1.73 m²). In one child we observed an improvement in eGFR from 43 to 67 ml/min/1.73 m² and reversal of papillary oedema whereas in the remaining 4 children the eGFR remained stable. None of the children had acute rejection and there were no infectious complications during the follow-up period. The mean cholesterol level increased from 4.84 to 5.25 mmol/l. No other adverse effects were reported.

Conclusions: Although we observed a clear short term benefit of CNI replacement in only one out of 5 children, this immunosuppressive regimen can prove beneficial in the long term due to the lower risk of nephrotoxicity. Further studies are required to establish the role of everolimus in paediatric renal transplantation.

PS1-THU-217

Outcome of severe Henoch-Schönlein nephritis (SHSN) in childhood traited with methylprednisolone pulses (MPP)

C. Samaille*¹, M. Dehennault¹, A Lahoche¹, R. Novo¹, M. Foulard¹

¹Pediatric Nephrology, Jeanne de Flandres Hospital, Lille Hospital, Lille, France

Objectives: There is not yet consensus on SHSN treatment strategies and from previous studies the rate of progressive renal insufficiency approaching 20% in the long term follow up. The aim of this retrospective study was to determine the pourcentage of end stage renal failure and SHSN remission at one year and at the end of the follow up of our cohort of patients treated in the North of France since 1980–

Patients and methods: 57 SHSN pediatric patients (mean age: 8.18 years) treated with MPP were retrospectively reviewed over the last 30 years. Severe HSN was defined at the onset as follow: proteinuria/creatininuria >1 g/g, proteinuria >1 g/L or 20 mg/Kg/d. Regimen include 3 MPP: 1 g/1.73 m² + prednisolone orally at the starting dose of 30 mg/m²/d for a month changed to alternate day for a month and slowly tapered thereafter. Cyclophosphamide (CYC-P) was started in persistent proteinuria. Remission was defined as a protU/creaU < 0.2.

Results: 57 patients with severe nephritis: mean protU/creaU ratio 6.19 g/g (1–22). 49% with nephrotic syndrome. 1 patient with acute renal failure and 20 with glomerular filtration rate between 60 and 90 ml/min/1.73 m2. No patient with renal failure at one year and at long term follow up (mean 3.5 years) (0.7–11.8 years). Remission at one year is obtained in 39/57 (68%) of patients and final remission in 43/57 (75%). 14% of patients were in remission but proteinuria reappears later. Corticosteroids alone obtained remission in 60% at one year and 58% at the long term. 20/57 patients received other treatment: CYC-P for 9/57 (16%), second MMP, cyclosporine, CYC-P and cyclosporine and/or IEC/ARA2. 10/20 are in remission at the long term.

Conclusion: We concluded that MMP is very effective and safe for the treatment of SHSN and should be considered as the first-line treatment of SHSN in childhood.

PS1-THU-224

Post-transplant anemia in children: still a continuing problem

B. Gülhan*¹, R. Topaloğlu¹, Y. Bilginer¹, T. Aki², F. Özaltın¹, A. Düzova¹, S. Özen¹, N. Beşbaş

¹Hacettepe University Pediatric Nephrology Department, Ankara, Turkey, ²Hacettepe University Department of Urology, Ankara, Turkey

Objectives and study: Anemia is a significant complication of chronic kidney disease (CKD) expected to resolve after renal transplantation. In present study, we investigated the prevalance of post-transplant anemia in a tertiary referral center.

Methods: There were 33 patients in 2011 that actively followed in transplantation unit. A cross-sectional study of these patients was performed. Data pertaining CKD etiology, growth, medications, dosage and serum levels of cyclosporine, tacrolimus and sirolimus, current serum creatinine, hemoglobine and hemotocrite levels were collected. Anemia was defined according to Kidney Disease Outcome Quality Initiative guidelines as Hb level <11 g/dl. Severe anemia was defined as Hb levels <10 g/dl.

Results: 33 renal transplant patients (23 from living related donor and 10 from cadavers) included in the study. The age range of patients was 4.3–17.6 years, mean and median values were 13.4 and 14.1 years, respectively. Mean duration of follow-up after renal transplantation was 29.6 months (1–99 months). 9 out of 33 patients have Hb levels lower than 11 g/dl. None of the patients have severe anemia. There was also no significant difference among anemic and non-anemic groups with regards to age, cause of renal failure, preemptive transplants, donor type, serum creatinine level and creatinine clearance. Anemia status according to immunsuppressive protocol was not statistically different. Most of the patients (17/33) were taking prednisolone, mycophenolate mofetil and tacrolimus and 2 of them have anemia. On the other hand six patients were taking prednisolone, mycophenolate mofetil and cyclosporine A and three of them have anemia. The difference of dosage and through levels of immunosuppressive drugs between anemic and non-anemic groups did not reach statistical significance.

Conclusion: Anemia was persisted in a substantial proportion of pediatric kidney transplant patients.

PS1-THU-226

Hyperuricaemia is associated with hypertension, obesity and albuminuria in children with chronic kidney disease

D. Noone*¹, S.D. Marks¹

¹Department of Paediatric Nephrology, Great Ormond Street Hospital for Children

Objectives and study: We assessed the prevalence of hyperuricaemia in a cohort of paediatric patients with chronic kidney disease (CKD) to establish a relationship between serum urate, renal function, body mass index (BMI), blood pressure (BP) and proteinuria.

Methods: Prospective study of clinical and laboratory data in CKD patients examining the relationship between estimated glomerular filtration rates (eGFR), BMI and hyperuricaemia using both correlation and regression models.

Results: 116 children (61% male), aged 0.4 to 17 (median 6.5) years of whom 63% had primary diagnosis of CAKUT were included in the analysis. Patients’ BMI were 10.6–34.3 (median 16.8) with eGFR of 60 ± 25 mls/min/1.73 m², serum urate of 127–780 (median 306)μmol/l and UA:UC of 0.3–2256 (median 59)mg/mmol. The prevalence of hyperuricaemia in those with an eGFR <60 mls/min/1.73 m² was 70% (compared to 34% for those with an eGFR >60 mls/min/1.73 m², RR 0.5 (0.3–0.7), p < 0.0001). Children with hyperuricaemia were more likely to have an eGFR < 60 mls/min/1.73 m² than those with a normal urate (OR 4.6 (2.2–9.4), p < 0.0001). Children with hyperuricaemia were more likely to be hypertensive or on antihypertensive therapy (OR 2.1 (1–4.1), p = 0.03) and have an increased BMI (p = 0.0001), albuminuria (p = 0.0001), renal dysfunction with reduced eGFR (p = 0.0001) and hypertension (p = 0.004). There was a significant linear relationship between eGFR and urate with regression coefficient −2.4 (95% CI −3.3 to −1.6, p = 0.0001). There was a significant linear relationship between BMI and urate with regression coefficient 13.1 (95% CI 8.6–17.5, p = 0.0001).

Conclusions: 70% of children in our cohort with Stage III–V CKD had hyperuricaemia, which was associated with renal failure, hypertension, obesity and albuminuria. In view of the cardiovascular risks of hyperuricaemia in adult CKD patients, it may well be prudent to undertake further vascular studies in our paediatric population, and consider the use of modifiying this with uricosuric agents.

PS1-THU-234

Way to kidney transplantation from our centre

I. Bajusz*¹, K. Losonczi¹, A. Vissy¹, L. Szabo^1,2,3

¹Department of Pediatric Nephrology, Velkey László Child Health Centre, Borsod County Teaching Hospital, Miskolc, Hungary ²Department of Health Science, University of Miskolc, Miskolc, Hungary ³Postgraduate Institute of Pediatrics, University of Debrecen, Miskolc, Hungary

Many problems of urinary tract result in chronic renal failure. Pediatric nephrology as an independent department began the work in 1976. The population number is 150 000 under 18 years of age in Borsod County. Patients for dialysis were sent to the University of Debrecen from the beginning until 1991. Dialysis was started at1991 in the Department of Pediatric Nephrology in Miskolc. Our first patient had kidney transplantation in Budapest in 1996. 25 children had kidney transplantation until 2010. The cause of chronic renal failure was obstructive uropathy with urinary tract infection, or reflux nephropathy in 14 patients, 1 child had congenital nephrotic syndrome, 3 patients had Alport syndrome, 4 had chronic glomerulonephritis with unknown origin and 3 had congenital kidney hypoplasia. The average time before renal raplacement therapy was 10 years. The time of renal replacement therapy was between 0 and 2 years untill kidney transplantation. 3 children had living donor transplantation and they did not have renal replacement therapy. The first renal replacement therapy was hemodialysis in 3 patients and peritoneal dialysis in 19 patients. The average time in dialysis was 13 months. 3 patients have died after transplantation. One of them a week after of his transplantation, 2 of them with bacterial infection at home, a year later of their succesfull transplantation. We had two other patients who died before transplantation because their cardiac failure. An other 17 patients with conservative treatment of their chronic renal failure were sent to adult nephrology unit because of their age were over 18 years. 6 children had conseravtiv treatment of chronic renal failure in our outpatient unit.

Kidney transplantation is the final treatment of patient with chronic renal failure.

PS1-THU-235

A modification of Schwartz formula for enzymatic creatinine assay

R. Sękowska*¹, M. Roszkowska-Blaim¹

¹Chair and Department of Pediatrics and Nephrology, Medical University of Warsaw, Warssaw, Poland

Estimation of glomerular filtration rate according to the Schwartz formula (eGFR), based on serum creatinine (SCr) determined by Jaffe method, while enzymatic assays are widespread used results in an overestimated glomerular filtration rate. The precision of the calculation also depends on the reference method and the less of creatinine measurement standardization.

Objectives: The purpose of this study was to determine the value of the k coefficient for eGFR with enzymatic determination of SCr to find the formula that reflects the reference method.

Methods: The study group consisted of 88 children in mean age 12.35 ± 4.06 years with chronic kidney disease (stage 1–4). eGFR was calculated using the Schwartz formula: ${\text{eGFR}}\left( {{\text{mL}}/{ \min }/{1}.{73}{{\text{m}}^{{2}}}} \right) = {\text{k}} \times {\text{body}}\,{\text{length}}\left( {\text{cm}} \right)/{\text{SCr}}\left( {{\text{mg}}/{\text{dL}}} \right)$; the constant k was 0.55 for children aged 2–12 years and from puberty 0,55 for females and 0,7 for males, and compared with the reference clearance of technetium-diethylenetriaminepentaacetic acid (99mTc-DTPA). SCr was determined enzymatically. Statistical analysis: regression analysis, Bland-Altman plot, Student t-test for paired samples.

Results: The mean difference between eGFR and 99mTc-DTPA differed statistically from zero (p < 0.0001) and was −28.4 ml/min/1.73 m². The modified value of the k coefficient was determined using regression analysis for the body length/SCr ratio in relation to the 99mTc-DTPA. The 95% confidence interval [CI] of the k coefficient was 0.407– 0.453 in all studied children, 0.395–0.447 in girls and boys aged less than 13 years, and 0.426–0.527 in boys aged more than 13 years. The mean difference between creatinine clearance calculated with modified value of the k coefficient (eGFR mod) did not differ statistically from zero.

Conclusion: A modified value of the k coefficient, adequate to creatinine assay and age, should be used for calculations of eGFR.

PS1-THU-238

Acute kidney injury (AKI) in children with hematologic and oncologic diseases

A. Moczulska*¹, K. Zachwieja², J. Klęba¹, L. Lis¹, M. Gancarz¹, M. Miklaszewska², D. Drożdż2, E. Wierzchowska-Słowiaczek¹, W. Balwierz³, J.A. Pietrzyk¹

¹Dpt. of Pediatric Nephrology University Children’s Hospital of Cracow, Poland, ²Dpt. of Pediatric Nephrology, Dialysis Unit, University Children’s Hospital of Cracow, Poland, ³Dpt. of Ped. Hematology a. Oncology, University Children’s Hospital of Cracow, Poland

Objectives and study: AKI remains a common complication in children during treatment of their hematological diseases. The aim of the study was to review and analyze the indications for renal replacement therapy(RRT) and it’s outcome in children with hematologic and oncologic diseases. The study group consisted of 18 children (8 girls and 10 boys) aged 3–18 years (mean 12 yrs.)who underwent RRT during chemiotherapy.

Methods: Appropriate treatment protocols were used for acute lymphoblastic leukemia(n = 8), acute myeloblastic leukemia(n = 2), chronic myelogenous leukemia(n = 1), Hodgkin\’s disease(n = 1), non-Hodgkin lymphoma(n = 5) and ovarian cancer(n = 1).Introduced RRT was: hemodialysis(n = 12), hemodiafiltration(n = 2), hemofiltration(n = 2), therapeutic plasma exchange(n = 2).

Results: Indication for RRT were as follow: rapidly increasing AKI signs or symptoms (eGFR <35 ml/min./1.73 m² and/or anuria <0,3 ml/kg/h) in 11 children mostly with sepsis and/or multi organ failure(MOF), tumor lysis syndrome in 2pts, drug toxicity in 3pts(methotrexate and NSAID), fluid overload with severe oedema-in 2pts.

RRT was successful in 14 patients(78%). 4 children(22%) died during RRT treatment-in this group treatment was introduced lately in advanced stages of MOF. One patient with ovarian cancer developed renal insufficiency with signs of Fanconi syndrome after 8 months of chemotherapy with cisplatin and ifosphamide and required chronic hemodialysis treatment for 15 months. Nowadays, she remains in CKD st.4.

Conclusions: In the study group generalized infection and /or MOF(61%) had been found as main indications for RRT to start. The RRT seems to be very helpful and effective in intensive paediatric oncology care, especially when introduced early. Late introduction of RRT was less successful. Signs and symptoms of Fanconi syndrome may be late presenting but rare adverse effect of chemotherapy.

PS1-THU-243

First paediatric experience of near-infrared spectroscopy (NIRS) as a continuous real-time monitoring for kidney graft perfusion

E. Vidal*¹, A. Amigoni², M. Fontanin², M. Varagnolo³, E. Benetti¹, G. Ghirardo¹, L. Murer¹

¹Nephrology, Dialysis and Transplant Unit, Department of Pediatrics, University of Padua,Italy, ²Paediatric Intensive Care Unit, Department of Pediatrics, University of Padua, Italy ³Department of Laboratory Medicine, University-Hospital, Padua, Italy

NIRS is a non-invasive technique to study tissue oxygenation. Its employment has been validated for cerebral perfusion monitoring in neonates. The purpose of our study was to investigate the role of NIRS in monitoring for kidney graft perfusion up to 72 hours post-transplantation (Ktx). Consecutive children undergoing living related (LR) or deceased donor (DD) Ktx were prospectively enrolled.

The values of renal regional oxygen saturation index (rSvO2) have been correlated with clinical (hourly urine output) and biochemical (serum creatinine and urinary neutrophil gelatinase-associated lipocalin [NGAL], both collected every 12 hours for 3 consecutive days) markers of adequate renal perfusion. Color Doppler ultrasonography (CDUS) was performed daily to assess global renal perfusion and intrarenal resistive index (RI).

Fifteen children were included, 4 underwent a LR-Ktx and 11 a DD-Ktx. Median age at Ktx was 9.2 years (1.6–17.8). The IS regimen consisted of prednisone with tacrolimus and MMF. No children experienced delayed graft function. In all patients CDUS showed normal vascularisation patterns and RI (median 0.63). Basal rSvO2 values were lower in DD-Ktx (median 65) compared with LR-Ktx (median 85; p < 0.05). In all DD-Ktx cases a relative increase of rSvO2 values from baseline was found after 72 hours (median 80; 67–95). During the 72 hours post-transplant of NIRS monitoring:- rSvO2 values showed significant correlation with both hourly diuresis (r = 0.7; p <0.05) and serum creatinine (r = −0.86; p <0.001);- NGAL exhibited a trend of decrease from baseline (median 297.35 ng/ml at baseline vs 35.7 at 72 hrs) in all DD-Ktx, with a significant negative correlation with rSvO2 (r = −0.75; p < 0.05). A less significant correlation (r = −0.36) was found in LR-Ktx, in which NGAL baseline values were lower (median 85 ng/ml).

Our results suggest that NIRS could become an adequate method for a real-time evaluation of kidney graft perfusion during the first hours after transplantation.

PS1-THU-248

Transplanting across ABO barrier: conditioning with rituximab and plasma exchange

M. Ognjanovic*¹, N. Moghal¹, H. Lambert¹, M. Coulthard¹, Y. Tse¹

¹Department of Paediatric Nephrology,Great North children Hospital,Newcastle Upon Tyne, UK

Objectives: We present our experience with 3 patients transplanting across ABO barrier, 2 of whom were conditioned with rituximab and Plasma exchange (PE).

Methods: A month prior transplant the patients received rituximab (365 mg/m² iv). A week before surgery each patient had 5 PE (on days 7, 5, 3, 2 and 1). Isoagglutinin titre (IgM and IgG) below 1:8 was consider safe to proceed with transplant. During each session double plasma volume was exchanged. After the last session the patient were given intravenous Immunoglobulin. We planned to do protocol post transplant PE (3 in total) on each patient. However, as we did not see an increase of isoagglutinins the patients were not routinely plasma exchanged post transplant.

Results: All three were sucessful transplants needing no further plasmaexchanges

Conclusions: Though our numbers are small we beleive conditioning with PE and rituximab can be used as an alternative to the more expensive immuno adsorptive columns (IAC). This may be important for the countries with limited resources. Also, most nephrology centres are familiar with PE.

PS1-THU-253

Comparing renal en bloc and single transplantation in pediatric donors and recipients: a review of 18 cases

C.A. Rogow*¹, S.L. Bergamo¹, M.C. Andrade¹, P.C.K. Nogueira¹, J.O.M. Pestana¹

¹Hospital do Rim e Hipertensão—UNIFESP, Sao Paulo, Brazil

End stage renal disease compromises growth and development in children. The therapy of choice is renal transplantation, but with shortage of donors, en bloc transplantation (EBT) from small donors has been used, though considered marginal. EBT with pediatric donors (PD) was previously described in adult recipients and involves high rates of technical complications. Data describing its use in pediatric recipients are limited, especially comparing EBT and single transplant (ST), which was the purpose of our study.

Patients <18 years who received EBT from PD at our institution between 2002–2007 were identified (n = 8) and compared with a control group (n = 10) matched according to age and sex, who received ST from PD. Surgical complications, graft losses and clinical outcome were compared. EBT and ST groups data were comparable: recipient age (14,4 ± 3,2 y vs 12 ± 5,1 y) and donor age (2,5 ± 1,1 y vs 2,8 ± 0,4 y). Acute graft loss due to thrombosis occurred in 3 patients from EBT (37.5%) and 1 patient (10%) from ST group. Late graft loss due to non compliance involved 1 patient of each group. Other surgical related complications included: fistula (1 patient of each group), dehiscence (1 patient in EBT group) and renal arterial stenosis (1/8 in EBT and 3/10 in ST group). One case from EBT group had surgically removed one of the kidneys due to distal ureteral necrosis (16 days after transplant). Survival curves showed 90% in ST vs 62,5% in EBT group at 3 years. EBT has more surgical complications that compromise short term graft survival but long term survival was the same as ST. The survival rates weren’t statistically significant but were clinically relevant. We reported one of the largest series of EBT in pediatric recipients, with 8 patients.

PS1-THU-259

Treatment of nephrotic syndrome recurrence after renal transplantation in children: the experience of one center in the north of France

R. Novo*¹, A. Lahoche-Manucci¹, M. Foulard¹, M. Dehennault¹

¹Pediatric Nephrology Unit, University Hospital of Lille, Lille, France

The recurrence of steroid-resistant nephrotic syndrome can lead to graft loss if patients do not receive any specific treatment.

We retrospectively studied 6 children (5 boys, 1 girl) who received transplants between December 2007 and October 2010, due to steroid-resistant nephrotic syndrome. The initial renal biopsy showed Minimal Change Disease in 4 cases and Focal Segmental Glomerular Sclerosis in 2 cases. The mean age at transplantation was 16 years 10 months (10 years 2 months to 19 years). All patients were treated with the same therapeutic strategy: a prolonged course of plasma exchange (PE), 2 to 4 weeks intravenous cyclosporine (until remission), and then oral cyclosporine therapy. The recurrence of nephrotic-range proteinuria occurred within the first 24 hours, in all 6 patients. Remission was obtained within 16.5 days (7 to 26 days). The first patient relapsed 3 months after a 12 months course of PE. For the remaining patients, PE was extended to 24 months without relapse. We compared these patients with 3 similar patients (1 boy, 2 girls), who received transplants between 2001 and 2003. The mean age at transplantation was 10 years and 3 months (6 years 4 months to 11 years 9 months). The therapeutic strategy was PE and oral cyclosporine therapy. Mycophenolate mofetil and steroids oral therapy was associated in both groups. In this former group, recurrence of nephrotic-range proteinuria occurred at different times (1, 8 days and four months). We obtained a sustained remission in only one patient after 10 PE’s during 3 weeks. The two other patients were PE dependant (one in complete, one in partial remission). This therapeutic association (PE, IV cyclosporine) was previously reported in pediatric series with success in 70% of patients. Our results in a small group confirm this success.

PS1-THU-260

Urinary metabolic values in a healthy Spanish children population

M.D. Rodrigo*¹, C. Saez –Torres², F. Grasses², G. Frontera³, A. Garcia⁴, C. Goméz⁴, A. Costa bauza², R. Prieto², J. Lumbreras¹, J. Figuerola¹

¹Pediatric Nephrology Unit. Hospital Son Espases, Palma de Mallorca, Spain ²Laboratory of Renal Lithiasis Research, IUNICS, Palma de Mallorca, Spain ³Stadistic department, ⁴Biochemistry Department Hospital Son Espases, Palma de Mallorca, Spain

Introduction: The investigation of urinary metabolic risk factors for lithiasis in children is dependent of the normal values. Due to the difficulty of obtaining a 24-h urine collection in children, comparison of the solute to creatinine ratios in random urine samples has been suggested as useful. Discrepant results are described depending if urine is obtained in a nonfasting or fasting period.

Objective: To determine values for urinary: Calcium/Creatinine, phosphate/creatinine, uric acid/creatinine, magnesium/creatinine, citrate/cretinine, oxalate/Cr and calcium /citrate ratio in a non fasting urine sample after scholar activity and to compare with solute/creatinine values in a 12 hours urine collection including night.

Materials: We studied 184 Spanish children aged 5 years to 12 years. From each subject isolated urine samples were collected at 07 pm before dinner, and 12 hour urine collection between 08 pm (after dinner) and 08 am (before breakfast).

Results: Urinary values are described as percentiles. Urinary P/Cr, Ur/Cr, Mg/Cr decreased with age. Median values of P/Cr, Ur/Cr, Mg/Cr, decreased from 1,16 mg/mg, 0,60 mg/mg and 0,15 mg/mg at 5 years to 0,58 mg/mg, 0,46 mg/mg and 0,08 mg/mg at 12 years in random urine samples. Ca/Cr, Citr/Cr and Ca/citr values were not affected by age. Their median values were 0,08 mg/mg, 705 mg/g and 0,11 respectively.Oxalate was only measured in 12-hour samples. In these samples, median values of P/Cr, Ur/Cr, Mg/Cr and Ox/Cr decreased from 1,20 mg/mg, 0,57 mg/mg, 0,2 mg/mg and 23,3 mmlo/mol at 5 years to 0,76 mg/mg, 0,42 mg/mg, 0,12 mg/mg and 14,4 at 12 years. Ca/Cr, Citr/Cr and Ca/Citr median values were 0,12 mg/mg, 539 mg/g and 0,22 respectively.

Conclusions: Correlation between urine ratios in both samples were good only for calcium and calcium/citrate. For the other solutes, that random urine values are not representative of those obtained in timed collections.

PS1-THU-261

Nephro.TV- internet TV provider by dialysis kids for dialysis kids

A. Mikolajczak*¹, E. Haffner¹, S. Brengmann¹, M. Bauer¹, J. Paffenholz¹, S. Habbig¹, B. Hoppe¹

¹University hospital of Cologne, Department of Pediatric Nephrology

Objectives and studies: Nephro.TV is a project by children and adolescents on maintenance (hemo)dialysis. It is the first project of its type in the world. Initiated in 2008 by the pediatric dialysis unit of the University Hospital Cologne it is not only used for entertainment during dialysis, but also to help them acquiring acknowledgement about their disease and to learn the handling of the new media. Public as well as friends and family members can get an impression of their skills and interests even on dialysis, so they get a realistic view on both sides of the disease: the suffering and their abilities. Hence, Nephro.TV is a further step towards modern care of chronically diseased children.

Methods: In close cooperation with editorial journalists ideas for TV Broadcasts are developed. The children perform inquiries, write presentations, perform film shooting as well as cutting and later bring all reports together for one broadcast every one to three months, which can be seen on https://doi.org/www.nephro.tv.

Results: A lot of informative reports have emerged during dialysis, yielding insight into sometimes delicate issues (e.g. waiting time, medication, compliance, living donation). They would otherwise probably neither been reported nor discussed in public.

Conclusions: It is necessary for children with and without chronic diseases, especially for older children, adolescents, teachers and instructors, to understand the problems of chronic renal failure. Nephro.TV helps them to get an idea of what it means to be chronically morbid: that they are not only victims of their disease but also experts in coping with it. They learn better about important topics of renal dysfunction and dialysis using modern media. That supports them to make an effort to be compliant. The children have to organise themselves and get a preparation for the future tasks.

PS1-THU-262

Comparison of the efficacy of recombinant human erythropoietin and darbepoetin alpha in the treatment of anemia in children with chronic kidney disease

C. Can¹, S. Emre*¹, I. Bilge¹, A. Yilmaz¹, A. Sirin¹

¹Istanbul University Istanbul Medical Faculty, Pediatric Nephrology Department, Istanbul, Turkey

Aim: Our aim was to compare the clinical efficacy of recombinant human erythropoietin (rHuEPO) and darbepoetin alfa (DA) in the treatment of anemia in children with CKD.

Methods: Thirty-four (13 female, 21 male) CKD patients receiving erythropoiesis stimulating agent (ESA) for at least six months were included in the study. Mean age was 11.42 ± 4.05 years. Seven patients (20.6%) were treated concervatively (CKD stage 4), 9 patients (26.5%) were on hemodialysis, and 18 (52.9%) were on peritoneal dialysis.

Results: Seventeen patients received rHuEPO and remaining 17 patients received DA. There was no significant difference between these groups when compared according to mean age, gender, dialysis modality, primary disease, drug application modalities, hemoglobin (Hb), hematocrit (Hct), ferritin and systolic-diastolic arterial blood pressure values at the beginning of the study (p > 0.05). Initial Hb levels of patients receiving DA and rHuEPO were 9.19 ± 0.68 gr/dl and 9.56 ± 0.56 gr/dl, respectively. Hb values were 10.35 ± 0.85 gr/dl in patients receiving DA and 10.67 ± 0.64 gr/dl in rHuEPO group at the end of the sixth month. Initial Hct levels of patients receiving DA and rHuEPO were 27.70 ± 2.18% and 29.01 ± 1.76%, respectively. Hct levels increased to 31.21 ± 2.85% in patients receiving DA and 32.28 ± 1.84% in patients receiving rHu EPO at the end of the sixth month. Hb and Hct values were not significantly different between the two groups during monthly follow up and at the end of the sixth month (p = 0.78 and p = 0.49, respectively) but there was a significant increase within each group (p = 0.03 for rHuEPO group; p = 0.04 for DA group). Hb values were not different between the patients who were receiving dialysis and were not receiving dialysis in DA (p = 0,84) and rHuEPO (p = 0,93) groups at the end of the study. The efficacy of subcutaneous and intravenous administration were similar within each group (p = 0.99 for DA group and p = 0.98 for rHuEPO group). Systolic hypertension was observed in only one patient in DA group, no other adverse effect was observed in either groups.

Conclusions: DA therapy can be an alternative to rHuEPO in the treatment of anemia in pediatric CKD patients with its clinical efficacy, application convenience, patient compliance and tolerability.

PS1-THU-266

Is combination of AT-III and heparin better than heparin to prevent fibrosis in experimental peritonitis?

E. Comak¹, S. Cengiz², T. Yilmaz², I. Bato², H. Akbas³, C.S. Dogan¹, A. Uslu Gökceoglu¹, M. Koyun¹, S. Akman*¹

¹Akdeniz University Medical Faculty, Department of Pediatrics, Division of Pediatric Nephrology, Antalya, Turkey, ²Akdeniz University Medical Faculty, Antalya, Turkey, ³Akdeniz University Medical Faculty, Department of Biochemistry, Antalya, Turkey

Aim: To compare the effects of anti-thrombin III (AT-III) and heparin on the development of peritoneal fibrosis in experimental peritonitis.

Methods: 40 rats that developed peritonitis by intraperitoneally (i.p.) injection of Staf. Aureus and were administered peritoneal dialysis solution i.p. for 14 days, were equally divided into four groups as they received either saline (control group), heparin (10 Units), AT-III (15 Units) or both heparin and AT-III (combination group). At the 14th day of the study, all rats were sacrificed, after when serum and dialysate samples were taken to study tissue-type plasminogen activator antigen (t-PA), plasminogen activator inhibitor type I antigen (PAI-1), thrombin-antithrombin III (TAT) complex, interleukin-1β (IL-1β), transforming Growth Factor-β1 (TGF-β1), transforming Growth Factor-β receptor (TGF-β1R), matrix metalloproteinase-2 (MMP-2), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF) and osteopontin (OPN). Also, inflammation and fibrosis scoring of peritoneal tissue were performed histopathologically.

Results: Serum and dialysate levels of MMP2, a profibrotic protein, and TAT complex, a marker of active coagulation, were higher in heparin group than combination group (p = 0.047, p = 0.004 and p = 0.005, p = 0.0001, respectively). Also, plasma and dialysate levels of tPA, an anti-coagulant protein, were higher in AT-III group than control group (p = 0.006 and p = 0.03). No statistically significant difference was found between the groups for other biochemical parameters as well as for inflammation and fibrosis scoring.

Conclusion: It seems that combination of AT-III and heparin is more effective than heparin to prevent fibrosis in experimental peritonitis.

PS1-THU-269

BK virus in renal transplantation: is primary renal disease with urinary stasis a risk factor?

A.E. Kuybulu¹, D. Mutlu², A. Uslu Gökceoglu¹, E. Comak¹, C.S. Dogan¹, M. Koyun*¹, S. Akman¹

¹Akdeniz University, Medical Faculty, Department of Pediatrics, Division of Pediatric Nephrology, Antalya, Turkey, ²Akdeniz University, Medical Faculty, Department of Microbiology, Antalya, Turkey

Aim: The aim of this study was to compare BK viruria, viremia and nephropathy in pediatric renal allograft recipients with and without structural or functional urinary tract abnormalities.

Methods: Pediatric renal allograft recipients who were followed up between January 2006 and January 2011 at our department were reviewed. Patients were divided into two groups according to the primary renal diseases as group I with urological anomalies such as posterior urethral valve, vesicoureteral reflux, neurogenic bladder and other obstructive uropathies, and group II consisting of patients with renal diseases other than urological anomalies such as glomerular, cystic and metabolic renal diseases. Urine and blood were collected to study BKV by polymerase chain reaction method biweekly for post-transplant first three months, monthly between 3–6 months and trimonthly thereafter. BK viruria and viremia was defined as >107 and >104 copies of BK virus DNA in urine and plasma, respectively. BKV nephropathy (BKVN) was confirmed histopathologically.

Results: A total of 122 children, 68 (55.7%) males, aged 15.0 ± 3.9 (3–22) years, were included. 53 (43%) and 69 (57%) patients were in group I and II, respectively. BK viruria, viremia and BKVN was detected in 26 (21.3%), 17 (13.9%) and 5 (4%) patients, respectively. No statistically significant difference was found between the two groups in the frequency of both viruria (34% vs 36.2%, p = 0.79) and viremia (26.4% vs 17.4%, p = 0.23). Among five patients with BKVN, 4 and 1 were in group I and II, respectively.

Conclusion: Urological anomalies as a primary disease do not seem to be a risk factor for the development of BK viruria and viremia in pediatric renal allograft recipients.

PS1-THU-270

BAFF/BAFF-R axis is dysregulated in patients after pediatric renal transplantation

A. Lehnhardt*¹, F. Dunst¹, M. Koch², M.J. Kemper¹

¹University Medical Center Hamburg-Eppendorf, Paediatric Nephrology, Hamburg, Germany ²University Medical Center Hamburg-Eppendorf, Hepatobiliary Surgery and Transplantation, Hamburg, Germany

Introduction: Not much is known about the influence of immunosuppressive regimes after paediatric renal transplantation on B-cells, which are increasingly recognized as important players in graft rejection. The B cell-activating factor of the TNF family BAFF and its receptor (BAFF-R) are crucial for B-cell survival.

Patients and methods: We performed a cross-sectional study of serum BAFF and BAFF-R expression on lymphocytes using flow cytometry and ELISA in a cohort of 44 children aged 12.3 ± 4.1 years after renal transplantation. Most patients (n = 27) received standard triple immunosuppressive therapy (CNI + MPA + steroids). 22 age-matched healthy children and 22 patients with endstage renal disease (ESRD) served as controls.

Results: Serum-BAFF levels were significantly higher in transplant patients compared to healthy controls (1435 ± 574 vs 894 ± 189 pg/ml, p < 0.001), not correlating with the observed reduced B-cell frequency in immunosuppressed children (11.3 ± 5 vs 17.1%, p < 0.001). BAFF-levels in ESRD-patients were higher than in healthy controls but comparable to renal transplant patients with a GFR >60ml/min (1233 ± 461 pg/ml vs. 1270 ± 369, ns) and significantly lower than in transplant patients with a GFR <60 ml/min (1233 ± 461 vs 1553 ± 447 pg/ml, p < 0.0435). Significant correlation of BAFF-levels with reduced BAFF-R expression on B-cells could be seen.

Conclusion: Immunosuppressive treatment after pediatric renal transplantation causes a reduction in B-cell numbers, but this cannot be regarded as sufficient explanation for elevated serum BAFF-levels which are observed, especially in patients with impaired graft function. Our data suggest an important role for BAFF in development of allograft dysfunction. Mechanisms and effects of BAFF/BAFF-R axis dysregulation and their value as diagnostic markers need to be investigated further.

PS1-THU-282

Antiviral prophylaxis with (VAL-)ganciclovir reduces the incidence of Epstein-Barr virus primary infection after paediatric kidney transplantation

B. Höcker* ¹, S. Böhm², M. Pohl³, U. John⁴, M. Kemper⁵, H. Fehrenbach⁶, M. Wigger⁷, M. Holder⁸, M. Schröder⁹, B. Tönshoff¹

¹University Children’s Hospital Heidelberg, Germany, ²Hygiene Institute Heidelberg, Germany, ³University Children’s Hospital Freiburg, Germany, ⁴University Children\’s Hospital Jena, Germany, ⁵University Children’s Hospital Hamburg, Germany, ⁶Children’s Hospital Memmingen, Germany, ⁷University Children’s Hospital Rostock, Germany, ⁸Olga Children’s Hospital Stuttgart, Germany, ⁹Clementine Children’s Hospital Frankfurt/Main, Germany

Objectives and study: Primary Epstein-Barr virus (EBV) infection constitutes a serious risk for paediatric transplant recipients, in particular regarding the development of EBV-related post-transplant lymphoproliferative disorder (PTLD). Currently, there is no established prophylactic regimen.

Methods: We therefore investigated whether an antiviral chemoprophylaxis with valganciclovir (VGCV) or ganciclovir (GCV) might reduce the incidence of EBV primary infection in EBV-naïve paediatric renal transplant recipients (R−), who had received a graft from a EBV-positive donor (D+) and are therefore at high-risk.

Results: Twenty-eight R-/D+ patients from a prospective, multicenter trial (n = 106) were categorized into an antiviral-prophylaxis (n = 20) and a control group (n = 8). Over the 1-year study period, 17/28 (61%) patients developed EBV primary infection, 10/28 (59%) showing EBV-related clinical symptoms (n = 6 flue-like symptoms, n = 2 infectious mononucleosis, n = 2 monomorphic B-cell PTLD). Antiviral prophylaxis with VGCV- or GCV decreased significantly the incidence of EBV primary infection: 9/20 patients (45%) in the prophylaxis group experienced an EBV primary infection compared to 8/8 patients (100%) in the control group; p < 0.0001). Chemoprophylaxis also resulted in a significantly lower EB viral load (p < 0.001) and less frequent EBV-related flue-like symptoms (p = 0.038). Type and intensity of immunosuppression, quantified according to the Vasudev score, neither had an effect on the incidence of EBV primary infection nor on the level/persistence of EB viral load or clinical symptoms. VGCV- or GCV were well tolerated.

Conclusion: Hence, chemoprophylaxis with VGCV or GCV markedly reduces the incidence of EBV primary infection in high-risk paediatric kidney transplant patients, thereby hopefully decreasing the risk for EBV-related PTLD.

PS1-THU-283

Multicentre, prospective trial on the incidence and morbidity of Epstein-Barr virus (EBV) infection after paediatric renal transplantation (RTX)

B. Höcker* ¹, S. Böhm², M. Pohl³, U. John⁴, M. Kemper⁵, H. Fehrenbach⁶, M. Wigger⁷, M. Holder⁸, M. Schröder⁹, B. Tönshoff¹

¹University Children’s Hospital Heidelberg, Heidelberg,Germany, ²Hygiene Institute Heidelberg, Heidelberg, Germany, ³University Children’s Hospital Freiburg, Freiburg, Germany, ⁴University Children’s Hospital Jena, Germany, ⁵University Children’s Hospital Hamburg, Hamburg, Germany, ⁶Children’s Hospital Memmingen, Memmingen, Germany, ⁷University Children’s Hospital Rostock, Rostock, Germany, ⁸Olga Children’s Hospital Stuttgart, Stuttgart, Germany, ⁹Clementine Children’s Hospital Frankfurt/Main, Germany

Since incidence and morbidity of EBV infection in children after RTx have been characterized insufficiently, we conducted a prospective, multicentre study on the incidence and course of EBV primary infection or reactivation in 106 patients during the 1st post-transplant year. 83% paediatric and 82% adult donors were EBV seropositive. 41% patients were EBV-naïve at time of RTx. 63% developed EBV primary infection, 46% reactivation. Patients with primary infection showed a high (18/27 vs.10/29,p = 0.03) and/or persistent (22/27 vs.5/29,p < 0.001) viral load (VL) significantly more often than those with EBV reactivation. In patients with primary infection, mean VL was 2.72 ± 0.93 vs. 0.33 ± 0.10 × 104 genomes/ml in those with reactivation (p = 0.01). 11% had no seroconversion despite primary infection. Whereas 17/27 (63%) patients with primary infection exhibited clinical symptoms (flue-like, n = 12; mononucleosis, n = 2; PTLD, n = 3), only 3/29 (10%, p < 0.001) with EBV reactivation were symptomatic. 8/18 (44%) patients were asymptomatic despite a high, persistent VL. 3/106 (2.8%) patients developed a monomorphic B-cell PTLD. The type of calcineurin-inhibitor did not influence the incidence of EBV primary infection/reactivation. 30% Tac- vs. 22% CsA-treated patients underwent primary infection (p = 0.45), 25% (Tac) vs. 26% (CsA) reactivation (p = 0.91). Patients undergoing EBV primary infection after RTx show clinical symptoms and a high and persistent VL significantly more often than those undergoing EBV reactivation. Conclusion: The observation that, on the one hand, patients with a high, persistent VL may remain asymptomatic for months to years, and that, on the other, those with low-level VL may contract EBV-associated PTLD indicates the low predictive value of high EB VL for PTLD development.

PS1-THU-287

Case report of a seriuos adverse event (SAE) following the administration of cinacalcet for secondary hyperparathyroidism (SHPT) in a child on chronic peritoneal dialysis (CPD)

E. Giardina¹, E. Verrina* ¹, K. Perri¹, G. Cangemi², E. Bottazzi³, O. Della Casa Alberighi⁴

¹Italian Registry of Pediatric Dialysis, Nephrology Unit, G. Gaslini Children’s Hospital, Genoa, Italy, ²Central Analytical Laboratory, G.Gaslini Children’s Hospital, Genoa, Italy, ³Central Pharmacy, G.Gaslini Children’s Hospital, Genoa, Italy, ⁴Clinical Pharmacology and Paediatric Clinical Trial Office, G. Gaslini Children’s Hospital, Genoa, Italy

Objectives and study: An unexpected SAE—i.e. recurrent liver function test alteration—occurred in a child on CPD exposed to cinacalcet within a clinical trial aimed at evaluating dose response and safety in the treatment of children with chronic renal failure (CRF) associated SHPT.

Methods: R.S. is a preterm born male child who had been on CPD and tube feeding for CRF due to renal dysplasia since his birth. At the age of 2.5 years (BW 11.5 kg), he presented with SHPT not responsive to standard therapy with vitamin D analogues and phosphate-binders, and was started on cinacalcet at an initial dose of 0.5 mg/kg/day per os. After first dosing, PK evaluation was performed. During the six-month pre-study screening he had presented high PTH values with serum calcium and phosphate levels in the normal range in absence of liver function test (LFT) alterations (AST 25 U/L; ALT 17 U/L;GGT 22 U/L). As per study protocol, LFT evaluation was performed monthly. Concomitant therapy included stable doses of amoxicilline, ranitidine, oxybutine, and erythropoietin.

Results: Since the first month of cinacalcet treatment, patient showed LFT abnormalities with AST 210 U/L, ALT 520 U/L and GGT 524 U/L. Hepatotropic virus search was negative. Ultrasound scan showed hepatomegaly. Following cinacalcet discontinuation, LFT returned to normal range within 30 days. Half dosing of cinacalcet (0.25 mg/Kg/day) was re-started leading to recurrent liver enzyme increase (AST 259 U/L, ALT 317 U/L, and GGT 164 U/L) one month later. Thereafter, cinacalcet was permanently discontinued.

Conclusions: Stringent LFT monitoring is advisable during cinacalcet treatment of very young children, for whom initial dosing is still empirically determined. Optimization of cinacalcet dose suitable for each pediatric patient is a challenge for this study and could be achieved through the PK evaluation.

PS1-THU-289

Growth cartilage expression of GH/IGF-I axis in spontaneous and growth hormone induced catch-up growth

I. Brito* ^1,2, H. Gil-Peña³, I. Molinos³, E. Garcia³, T. Henriques-Coelho^2,4, A. Caldas-Afonso^2,4, F. Santos³

¹Pediatric Reumathology Unit, Pediatric Department, Hospital São João, Porto, Portugal, ²Faculty of Medicine, Porto, Portugal, ³Department of Pediatrics, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain, ⁴Pediatric Department, Hospital São João, Porto, Portugal

Introduction: Catch-up growth is a well know phenomenon that can be affected by several pathological conditions like chronic renal failure. A recent hypothesis proposes an intrinsic essential mechanism for catch-up growth in the long bones growth plate (GP).

Aim: The present study was designed to determine if the ability to exhibit catch-up growth is related to alterations on the local growth-hormone (GH)-IGF-I axis modulation as well as to evaluate the effect of GH treatment on this process.

Material and methods: Female Sprague-Dawley rats with 25 days of age were randomly grouped: normal renal function and no diet restriction (group C), animals with normal renal function and diet restriction (group CR) and animals with normal renal function, diet restriction and GH treatment (group CRGH). After refeeding, analysis of GH-R, IGF-I, IGF-I R and IGFBP-5 expression by real-time PCR was performed at the time of catch-up growth identified by osseous front advance greater than that of C animals.

Results: In the absence of GH treatment, catch-up growth was associated with increased mRNA IGF-I and IGFBP5 levels, without changes in GHR or IGF-IR. GH treatment maintained the overexpression of IGF-I mRNA and induced an important increase in IGF-IR expression at the growth plate.

Conclusions: After diet restriction, catch-up growth might be related with a dual stimulating local effect of IGF-I in growth plate, as a result of overexpression of IGF-I and increased bioavailability through IGFBP5. GH treatment preserved these mechanisms and potentiated local IGF-I actions by increasing IGF-IR expression. Future studies of local GH/IGF-I axis in chronic kidney disease models are necessary to better understand the abnormal catch-up growth pattern found in this disease.

PS1-THU-293

The use of transferrin receptor ferritin index to diagnose iron deficiency in pediatric renal transplant patients

A. Tsampalieros* ¹, N. Lepage², J. Feber¹

¹Department of Pediatrics, Children’s Hospital of Eastern Ontario, ²Department of Genetics, Children’s Hospital of Eastern Ontario

Objectives: Serum ferritin and transferrin saturation (TSAT) are used to diagnose iron deficiency (ID) but can be affected by inflammation. As children with chronic kidney disease post kidney transplantation (Tx) often have low grade inflammation, these markers may not be reliable. A ratio of serum soluble transferrin receptor to log ferritin (TRFI) has been proposed as a new marker of ID, less dependent on inflammation. The objective of this study was to compare the detection rate of ID using TRFI and ferritin + TSAT.

Methods: All available serum ferritin, TSAT and TRFI values were collected from the post Tx follow-up period. At each visit, ID (defined as ID event) was assessed based on KDOQI criteria (ferritin <100 μg/L and TSAT <20%) and TRFI >0.6*. The ID events were then pooled; agreement/disagreement in the detection of ID between two methods were analyzed with Chi-Square statistics.

Results: Data were obtained from 21 children (11 males) aged 1.6 to 16.7 years. Median Schwartz GFR was 63.18 mL/min/1.73 m² at last follow-up; 80% of patients received iron supplementation. A total of 133 blood samples over 2.4 ± 1.3 years of follow-up were analyzed. KDOQI and TRFI agreed on detection of ID on 33 occasions and agreed on absence of ID on 32 occasions. TRFI detected 67 additional ID events whereas KDOQI detected ID on only 1 occasion (Chi-square = 11.71, p = 0.0006, odds ratio = 15.76, 95% (CI 2.07–120.5).

Conclusion: The transferrin receptor ferritin index significantly increased the detection rate of iron deficiency as compared to KDOQI definition. It appears to be a more sensitive marker of iron deficiency in renal transplant patients.

*Horl, Walter. J Am Soc Nephrol 200718: 382–393

PS1-THU-299

Reference values of creatinaemia in ELBW neonates following either Jaffe or enzymatic analysis

M. Kuppens* ¹, D. Mekahli², Z. Zaman³, F. Vanstapel³, C. Vanhole⁴, J. N. van den Anker⁵, E. Levtchenko², K. Allegaert⁴

¹Department of Paediatrics, University Hospitals Leuven, Leuven, Belgium, ²Department of Paediatric Nephrology, University Hospitals Leuven, Belgium, ³Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium, ⁴Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium, ⁵Department of Paediatrics, Erasmus MC Sophia Children’s Hospital, Rotterdam, The Netherlands

Introduction: Serum creatinine (Scr) depends on the technique applied. We report reference values (median/P25–75/P90, mg/dl) in ELBW cases following Jaffe colorimetry or enzymatic quantification.

Methods: Postnatal Scr (day 1,2,3,7,14,21,28) in a cohort of 151 ELBW cases (Jaffe) [1] was compared to 116 ELBW cases (enzymatic) with similar (weight, age) characteristics.

Results: For Jaffe, (consecutive days) 0.75/0.67–0.87/1.02, 1/0.89–1.13/1.3, 1.09/0.97–1.22/1.34, 0.87/0.74–1.02/1.18, 0.77/0.68–0.9/1.07, 0.77/0.68–0.9/1.07, 0.68/0.61–0.76/0.89, 0.61/0.55–0.67/0.76, 0.61/0.55–0.67/0.76. For enzymatic, Scr was 0.575/0.5–0.68/0.92, 0.85/0.74–0.93/1.06, 0.91/0.81–0.99/1.11, 0.735/0.63–0.86/1.06, 0.55/0.47–0.63/0.71, 0.44/0.38–0.51/0.60, 0.41/0.36–0.46/0.54.

Conclusions: Simple conversion from Scr Jaffe to Scr enzymatic based on one single absolute difference is inadequate in ELBW neonates. The technique to measure creatinaemia is of clinical relevance; reference values in ELBW cases are provided. [1] George I, et al. Renal Impairment in ELBW Infants Can Be Defined on Day 3. Pediatric Nephrology 2010: 25(9):1973 (abstract 892).

PS1-THU-301

Successful treatment with IVIG and rituximab for treatment of chronic antibody-mediated rejection in pediatric renal transplant recipients

H. Billing*¹, C. Suesal², J. Ovens², R. Waldherr³, G. Opelz²

¹University Children’s Hospital Heidelberg, Germany, ²University Children’s Hospital Heidelberg, Department of Transplantation Immunology, Heidelberg, Germany, ³Institute for Clinical Pathology, Heidelberg, Germany

Background: Resent studies have shown (El-Zoghby et al., AJT 2009) that chronic antibody mediated rejection (CAMR) is the major cause of late renal transplant loss. There is no established treatment protocol for this condition yet. We have published results of a pilot study in 6 pa-tients on treatment of CAMR with an antihumoral regimen consisting of high-dose intrave-nous immunoglobulin (IVIG) and rituximab (Billing et al, Transplantation 86, 2008). Here we report the data of 21 patients with CAMR.

Methods: 20 pat. (age 14 ± 6.4) with CAMR 5.8 years (1.2–13.8 years) after Rtx was treated with IVIG (4 × 1 g/kg KG per week) and Rituximab (1 dose à 375 mg/m2) and studied with a follow up of 12 mo. Response to therapy was defined as reduction of loss of GFR about 50% 6 mon. post therapy compared to 6 Mon. pre therapy. Renal allograft biopsies were evaluated using the Banff ‘05 classification. HLA-specific antibodies were detected by panel reactive lympho-cytotoxicity, solid phase ELISA assays and the Luminex assay.

Results: The average loss of GFR 6 mo pre therapy was 9,8 ml/min/1.73 m² (25–75% Perzentile, 12.7–4.5) and was stabilized 6 mo post therapy at 2.88 ml/min/1.73 m² [9.2 bis −4.6) (P = 0,0013). 11/20 pat. (55%) showed a response to therapy. Non-responder (n = 9) were associated with a histologic diagnose of transplantatglomerulopathy compared to responder (P = 0,012). Prior to antihumoral therapy, 16 of 21 patients showed de novo DSA. 6 mo after antihumural ther-apy, DSA were no longer detectable in 5 of 16 patients. Response to therapy was associated with DSA MFI >5000 . One patient developed PCP one year after rituximab.

Conclusion: This pilot study demonstrates that 55% of patients with CAMR can be treated successfully and safely with a combination of IVIG and rituximab. Patients with CAMR complicated by TG did not show a response to AHT.

PS1-THU-302

Persistent hyperparathyroidism after pediatric renal transplantation

K. S. Galleroglu*¹, E. Baskin¹, U. Bayrakci¹, S. Aktas², H. Karakayali², M.Heberal²

¹Baskent University Pediatric Nephrology, Department of Transplantation Immunology, Ankara, Turkey, ²Baskent University General Surgery, Anakra, Turkey

Hyperparathyroidism is a frequent complication of chronic kidney disease and persists after renal transplantation 25–43% of patients. Glomerular filtration rate less than 70 ml/min, use of cyclosporine A and low serum 25-OH D vitamin levels after transplantation are the risk factors of persistent hyperparathyroidism.

Forty-four pediatric renal transplant recipients with stable graft function were studied. Median follow-up time after transplantation was 17.5 months. None of the patients was treated with vitamin D or calcium supplements or had undergone previous parathyroidectomy. 29 patients received cyclosporine A, 15 patients received tacrolimus as immunosuppressive treatment. Also each patient received mycophenalote mofetil and oral prednisolone. Bone mineral densitometry of the lumbar spine was measured. The aims of our study were to examine the status of parathyroid hormone levels after transplantation and determine the clinical and biochemical risk factors of persistent hyperparathyroidism.

Fifteen patients have parathyroid hormone levels greater than 70 pg/ml. Mean serum bicarbonate level was significantly lower in patients with persistent hyperparathyroidism when compared with the other patients (respectively 18.9 ± 3.01, 21.8 ± 3.49, p < 0.05). A significant negative correlation was noted between parathyroid hormone level and serum bicarbonate level (r = −0.30, p = 0.044). Another significant negative correlation was shown between parathyroid hormone level and Z score (r = −0.31, p = 0.038). Mean serum calcium and mean serum phosphate levels were similar for high and normal parathyroid hormone levels. There was not any relationship between posttransplant parathyroid hormone levels and glomerular filtration rate, steroid doses, type of immunosuppressive regiment, fractional excretion of sodium and tubular phosphate reabsorption. In conclusion we assume that low serum bicarbonate level is one of the predictor of persistent hyperparathyroidism after renal transplantation.

PS1-THU-308

The value of early Doppler USG and DTPA in predicting late survival of transplanted kidneys

E. Melek¹, E. Baskin¹, U. Bayrakci¹, K. Gulleroglu* ¹, N. Uslu², A. Aktas³, S. Aktas⁴, H. Haberal⁴, M. Karakayali⁴

¹Baskent University Pediatric Nephrology, Ankara, Turkey, ²Baskent University Radiology, Ankara, Turkey, ³Baskent University Nuclear Medicine, Ankara, Turkey, ⁴Baskent University General Surgery, Ankara, Turkey

Doppler ultrasonography (DUSG) and Tc-99m-DTPA renal scintigraphy are useful diagnostic tools for the management after transplantation. However, the role of DTPA in predicting long term graft function has never been studied yet. 70 renal transplantated children were enrolled in the study. All patients were underwent DUSG and DTPA at 3rd and 7th Ptx days. The value of early Ptx DUSG and DTPA in predicting long term graft function was studied by means of renal function tests during follow-up. We have found that 96% of patients with low mean renal artery RI at Ptx 7th day have functioning graft at Ptx 5th year. However, only 81% of patients with RI >0.7 have functioning graft at Ptx 5th year (p < 0.05). We have found that 33% of patients with normal DTPA at Ptx 7th day and 66% of patients with abnormal DTPA have poor functioning graft at the end of Ptx 5th year (p = 0.03). 29.5% of patients with DTPA revealing GFR <60 ml/min have lost their graft while only 7.5% of patients with GFR >60 ml/min have lost their graft (p = 0.03).

50% of patients with DTPA uptake at Ptx 7th day <3.5 were found to have graft loss while only 11% of patients with uptake >3.5 (p = 0.04).

We did not find any significant relation between Ptx 3rdday DUSG, DTPA and long term graft survival. Parameters obtained by DTPA at Ptx 7th day have a significant predictive value about long term graft survival. We suggest checking renal functions by DTPA at Ptx 7th day

PS1-THU-311

The demographic characteristics of the paediatric chronic kidney disease population in south east England over a 5 year period

J.J. Kim* ¹, C. Booth¹, S. Waller¹, P. Rasmussen¹, C. Reid1, M.D. Sinha¹

¹Evelina Children’s Hospital, London, UK

Introduction: The Evelina Children’s Hospital is the sole tertiary nephrology unit covering South East England with a population of 1.541 million children. Our objective was to describe the demographics and to analyse changes in demographics over a 5-year period, in children with CKD stage 3b to 5.

Methods: Retrospective review of all children <18 years of age with eGFR <45 ml/min/1.73 m² who were managed at our unit from 2005 to 2009. GFR was estimated using Schwartz formula. We excluded all patients with current active kidney transplant. We included all infants with eGFR persistently <45 ml/min/1.73 m² on two measurements 1 year apart. Single eGFR measurements were performed at entry and subsequently at anniversary visits. CKD was defined as per KDOQI guidelines.

Results: 206 children (58.3% males) were managed over a 5 year period with a median (IQR) eGFR of 26.1 (15.8–35.9) ml/min/1.73 m². The mean incidence over the 5 year study period was 16.0 per-million age related population (pmarp) and the mean prevalence 75.9 pmarp. Incidence increased from 11.0 to 19.5 pmarp and the prevalence from 63.6 to 88.9 pmarp. Similar trends were observed even after excluding patients on dialysis. At point of entry, median (IQR) age and eGFR was 4.7 (0.2–12.2) years and 23.5 (8.6–37.4) ml/min/1.73 m² respectively. Dysplasia, glomerulonephritis and obstructive uropathy comprised 44.2%, 18.0% and 14.6% of all patients. Main ethnic groups included 66.0% white, 16.0% south asian and 10.2% black.

The mean prevalence over 5 years by CKD stage 3b, 4, 5 and dialysis was 23.6, 27.6, 12.8 and 11.8 pmarp respectively with an increase for stages 3b, 4 and dialysis over the 5 year study period. 37 (18.0%) children were transplanted, 21 (10.2%) transitioned to adult care and 7 (3.4%) died.

Conclusion: Our paediatric CKD 3b to 5 population has continued to expand slowly over the study period. The observed incidence and prevalence rates appear higher than other published series.

PS1-THU-313

Anaemia in children on chronic dialysis: a report from the Italian registry

S. Maringhini* ¹, C. Corrado¹, A. Edefonti², S. Picca², B. Gianoglio², T. De Palo², C. Pecoraro², G. Montini², E. Vidal², E. Verrina²

¹Pediatric Nephrology. “G. Di Cristina” Hospital, Palermo, Italy, ²Italian Pediatric Dialysis Registry, Italy

Objective and study: Anaemia is a common problem amongst children on dialysis, and is mainly due to decreased erythropoietin synthesis and iron deficiency. Therefore, therapy with erythropoiesis stimulating agents (ESA) and iron is largely used to achieve the recommended haemoglobin levels (Hb). In this study we report the data on anemia control from the Italian Registry of Pediatric Dialysis.

Methods: Information on Hb in children on hemodialysis (HD) and peritoneal dialysis (PD) have been collected since 2005. Data, at the time when dialysis was started, were available for a total of 105 children, between 6 month and 18 years of age; for 57 of them a 12 months follow-up was available as well.

Results: Mean ± SD of Hb was 10.1 ± 1.7 g/dl; ESA was already administered in 86 (82%) children who were older than the others (8.9 ± 6.1 vs 7.7 ± 7.7). Hb levels were comparable between patients on ESA or not (10.1 ± 1.6 vs 10.0 ± 1.7). Hb level was ≤10 g/dl in 45% of patients, and ≥12 g/dl in 12%; age, sex, PTH levels were comparable in these 2 groups. Data at 12 months were available in 51 children (37 males and 14 females; 26 on PD and 25 on HD). All except one received ESA and all except five iron. Since the start of dialysis, mean Hb levels had increased from 10 ± 1.8 to 11.1 ± 1.5 g/dl; Hb was ≤10 in 13% and ≥12 g/dl in 13%; of the first group 4 were females and only one was on PD.

Conclusions: Anemia is frequent in Italian children with chronic renal failure before dialysis is started, improves during dialysis, and is more frequent in females and in patients on hemodialysis.

PS1-THU-324

Comparable suppression of NFAT-regulated-gene expression in response to cyclosporine in pediatric vs. adult renal transplant recipients

H. Billing*¹, C. Sommerer³, T. Giese⁴, S. Meuer⁴, B. Tönshoff¹, D. Czock²

¹University Children’s Hospital Heidelberg, Germany, ²Institute of Pharmacology, University of Heidelberg, Germany, ³Department of Nephrology, University of Heidelberg, Germany, ⁴Institute of Immnunology, University of Heidelberg, Germany

Background: Many drug targets and metabolizing enzyme are developmentally regulated during childhood, (Kearns GL, NEJM 349, 2003). This is relevant for medications with a narrow therapeutic index. We investigated a potential developmental regulation for CsA in paediatric and adult renal transplant recipients. No in vivo data on this issue have been published yet.

Method: We analyzed in a prospective study 184 renal allograft recipients in the maintenance period post-transplant, age <18 y, 18–59 y and >=60 y (N = 31, 98, 55). Ciclosporin (CsA) concentrations were measured before and 2-hours (C2) after drug intake. Expression of IL2, INFγ and GMCSF was measured in PMA/ionomycin-stimulated peripheral blood lymphocytes by quantitative real-time PCR. Differences between groups were analyzed by the Kruskal Wallis test and Dunn’s test. The influence of age and CsA concentrations were analyzed by multiple linear regression analysis.

Results: Average C2 concentrations in younger patients were significantly (P < 0.01) lower (289 μg/L [25–75% Perzentile, 236–430]) compared to adults (456 μg/L [339–580] bzw. 524 μg/L [461–674]). Residual biomarker expression was inversely correlated to C2 concentrations (25% vs. 14% and 11%, p < 0.01). By multiple linear regression analysis residual IL2 expression in relation to CsA C2 blood concentration showed a 23% stronger inhibition (p < 0.01) in the group <18 years, while the suppression of INFγ, GMCSF or entire NFAT-regulated-gene expression in response to CsA was comparable.

Conclusion: We observed a higher sensitivity of residual IL2 expression in pediatric Ntx patients towards CsA of this particular cytokine. The overall suppression of NFAT-regulated-gene expression in response to CsA was comparable among age groups.

PS1-THU-327

The certain registry: a novel web-based registry for paediatric kidney transplantation in central Europe

L. Plotnicki^1,2, B. Höcker¹, C. Kohl3, B. Tönshoff*¹

¹University Children’s Hospital Heidelberg, Germany, ²Medical Informatics, University of Heidelberg/Heilbronn University, Heidelberg, Germany, ³Coordination Center for Clinical Studies, University of Heidelberg, Heidečberg, Germany

Objectives and study: Although long-term data collection for paediatric RTx recipients is crucial for clinical research, quality assurance and improved patient care, a proper registry in central Europe is lacking. In 2009, the German Society of Paediatric Nephrology (https://doi.org/www.gp-nephrologie.de) decided to fill this gap and initiate such a registry, which was named CERTAIN (Central European Paediatric Renal Transplant Initiative) Registry.

Methods: Data protection and security have been considered from the beginning. Therefore the registry has been developed as a distributed system. Its architecture assures the separation between personal and medical data on all levels incl. separate servers, strict data access policies and traffic encryption. This idea is based on the work of the German TMF—Technology, Methods and Infrastructure for Networked Medical Research organization (https://doi.org/www.tmf-ev.de). All registry functions are accessible via convenient web-application, hence, no extra software needs to be installed on-site. To minimize manual data input and workload in the participating centres, bidirectional data interchange with other systems, such as CTS, Eurotransplant and the ESPN registry has been realized.

Results: The CERTAIN Registry is enabling not only the long-term data collection of paediatric RTx patients but also provides the possibility of patient record creation, real-time data analysis, patient & clinic benchmarking and automatic calculation of relevant clinical values. Thanks to its modular design and use of state of the art technology, it can be easily extended with new features. The registry is online since October 2010 (https://doi.org/www.certain-registry.eu) and accessible for all RTx centres, who wish to participate.

Conclusions: The CERTAIN Registry provides a novel platform for clinical research in the field of paediatric RTx by use of modern IT methods, which will hopefully find a wide acceptance across Europe. First registry reports are planned for 2011.

PS1-THU-328

Is the effectiveness of continue venovenous hemodiafiltration related to rifle criteria and etiology of renal failure?

N. Dincel*¹, O.D. Kara¹, A. Keskinoğlu¹, S. Mir¹

¹Ege University Medical Faculty, Izmir, Turkey

Renal replacement therapy has evolved from the need to treat the dysfunction of a single organ.As intensive care units have become more and more complex, it has become clear that the majority of patients with acute renal failure (ARF) often have dysfunction of several other organs. In order to facilitate multi organ support, continue renal replacement therapy (CRRT) techniques have been developed. The proper goal in intensive care units (ICU) is, multiorgan support therapy.For this supporting therapy, continue venovenous hemodiafiltration (CVVHDF) is becomed commonly used.We aimed to mark the relationship between CVVHDF success and etiology of renal disease. Patients having CVVHDF in different ICUs during the last 2 year period, consulted with us were included to study. Patients with acute renal failure treated with other dialysis modalities were excluded to study. Clinical data of patients were collected from the charts of patients retrospectively. Their mean age, primary cause, time of HDF need, concultation time to us and duration time of HDF were noted.

Patients were classified into two groups according to their primary etiology of disease, as cardiac and non-cardiac group. Cause and severity of renal failure, were assesed at the time of HDF initiation. Stage of renal failure was evaluated according to RIFLE criteria. Outcome is categorized as primary and secondary. Primary outcome was accepted as the composite correction of uremia, acidosis and methabolic parameters, and regression of fluid overload. Secondary outcomes, were improvement of hemodynamic instability and survival. Clinical severity is classified according to the APACHE score. Also, cardiac exams, ventilatory need,stay lenght in ICU and cause of deaths were noted down.

Totally charts of 36 patients,with a mean age of 6.9 years, were scanned. The mean concultation time was 38.7 hours of ICU stay. There were 9 patients and 27 patients in group 1 and 2 respectively. The majority of diagnosis were total abnormality of major vessels, ventricular septal defects and tetralogy of fallot in group1. Whereas there were heterojenity of etiologies in gruop 2, such as; 2 cases of tumor lysis syndrome, 3 with methabolic diseases, 3 traumas, 4 multiorgan disease accompanied with sepsis, 1 meningococsemia, 1 acute renal graft rejection, 1 SLE activation. 6/9 patients of group 1 were in RIFLE class failure and 13/27 were in risk, 8/27 were in injury and the last 6 were in the failure class in group 2 when they consulted with us. The mean initiation time of CVVHDF were 2,8 hours after they had been consulted to us. They received 80.6 hours and 35 hours of dialysis, in group 1 and 2 respectively. As their responce is better in group1, dialysis time was shorter than the second group. Although no statistically significant differences were seen in primary outcome (88,8% in group1 and 85.1% in group 2; p > 0.05) between both groups, secondary outcome were less in group 2 ameliorately. This was due to the mortality rates which were 77,7% in group 1 and 51,8% in group 2(p < 0.01). High APACHE score , decreased cardiac ejection fraction, arthmias, longer need for ventilatory support, sepsis were frequent in cardiac patients even if they had not proceeded to acute renal failure or multi organ disease.

Our results showed that, CVVHDF treatment is successful even if in cardiac patients having with high mortality rate and been in the later stage of acute renal failure. We think that whenever these highly mortal cases were consulted in earlier stages of acute renal failure, secondary outcome of CVVHDF will be more succesfull as well as its primary outcome.

PS1-THU-333

Evaluation of serum zinc and copper in children with chronic kidney disease

D. Youssef*¹, A. Noseer¹, Y. Aboelmagd², A. Abdualla¹

¹Zagazig university, Paediatrics departement, Cairo, Egypt, ²Zagazig university, Biochemistry departement, Cairo, Egypt

Introduction: Trace elements may be further modified by the dialysis procedure and to prevent complications in chronic hemodialysis patients, it is important to know and regulate the levels of trace elements .The aim of this work is to evaluate the serum zinc (Zn) and copper (Cu) levels in children with chronic kidney disease.

Patients and methods: This is a “case control study” comprised; 20 children with chronic kidney disease (CKD) stage 5 on regular hemodialysis (8 boys and 12 girls; mean age: 11.75 ± 3.64 years) as group A, and the duration of the dialysis at the time of the study is between 12 and 96 months (mean: 20.97 ± 14.8 months), 20 children are with CKD stage 3 and 4 on conservative treatment (11 boys and 9 girls; mean age: 10.56 ± 3.19 years) as Group B children, and 10 children as control group C; (6 boys and 4 girls; mean age: 12.02 ± 3.18 years). All subjects are subjected to: Full history taking, Thorough clinical examination, Routine laboratory investigations; CBC, BUN and serum creatinine, serum iron concentration, determination of serum zinc level and serum cupper level; measurements of serum copper and zinc were performed by atomic absorption spectrophotometry. For patients on regular hemodialysis, we used predialysis samples.

Results: We found that serum Zn was (74.4 ± 12.6 μg/dl) in group A, (76.7 ± 13.5 μg/dl) in group B with no significant difference between both groups but they are both significantly lower than group C in which serum Zn was (97.7 ± 14.3 μg/dl). As regard Cu level it was (89.3 ± 15.1 μg/dl) in group A, (95.6 ± 16.2 μg/dl) in group B, while it was (116.6 ± 13.6 μg/dl) in group C with significant reduction of serum level in patients with CKD. In studying the correlation between Zn, Cu with other parameters either demographic or laboratory in our patients we found a significant negative correlation with urea, creatinine and serum iron level.

Conclusion: Serum zinc and copper levels are significantly decreased in patients with CKD when compared with healthy children. There is highly significant correlation between serum Zn and Cu when compared with serum iron in our studied groups.

PS1-THU-339

Not leaving home- continued care of adolescent and young adult kidney transplant recipients at the pediatric nephrology clinic

S. Feinstein*¹, E. Ben-Shalom¹, R. Becker-Cohen¹, C. Rinat¹, N. Meislish¹, Y. Frishberg¹

¹Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel

Transition of adolescents and young adults kidney transplant recipients to an adult nephrology service may lead to rates as high as 40% of graft loss due to non-adherence. The aim of the study was to evaluate the advantages of our approach, which is to continue providing care for this population unless they opted otherwise. Graft function, the prevalence of non-adherence to immunosuppressive (IS) medications, and various parameters of social adaptation were assessed in 64 patients, currently over 16 years of age (23.3 ± 5.4 yrs) and followed at our clinic for >1 year after kidney transplantation (KTx) (9.4 ± 4.8 yrs; 31 > 10 yrs, 11 > 15 yrs).

GFR 5, 10 and 15 years following KTx was 73.9 ± 25.7 (N = 43), 69.1 ± 24.75 (N = 31) and 63.4 ± 29.3 (N = 11) ml/min/1.73 m², respectively.

Non-compliance (NC) was defined as discontinuation of >1 IS medication or drug holidays. Patients’ self report and/or low CNI serum levels served as indicators of NC.

Non-adherence was documented in 11/64 (17.2%), all of whom were adolescents (15.7 ± 2.2 yrs at first episode). Three had recurrent episodes of NC at 20–24 yrs of age. In 6, NC resulted in late acute rejection with consequent graft loss. Two suffered from mental retardation (MR). With respect to patients >18 years, 26.8% are married, 16% have 1–4 children, each. 86% of all patients work (N = 27), study (11 - students, 9 attend high school), volunteer in the military (2) or are homemakers (6). Nine - are unemployed or work occasionally.12 patients with MR attend special education or work at a protected facility.

In conclusion, continued care of post transplant adolescents and young adults in the same pediatric nephrology clinic, which provides a long-term personal relationship with easy access to a permanent staff and interaction with peers, is one way to improve compliance, graft function and quality of life.

PS1-THU-341

Anemia in European pediatric transplant recipients; results from the ESPN/ERA-EDTA registry

L. Krischock¹, K.J. van Stralen*², E. Verrina³, J.W. Groothoff², J. Tizard⁴, K.J. Jager², F. Schaefer⁵

¹Royal Hospital for Sick Children, Glasgow, United Kingdom, ²Academic Medical Center, Amsterdam, The Netherlands, ³G Gaslini Hospital, Genoa, Italy, ⁴Bristol Royal Hospital for Children, Bristol, United Kingdom, ⁵University of Heidelberg Center for Pediatrics and Adolescent Medicine, Germany

Objectives and study: To determine the prevalence of anemia in children with a renal allograft, and to identify potential determinants associated with anemia within this population.

Methods: Data were derived from the ESPN/ERA-EDTA registry from 2192 children with a transplant, all aged less than 18 years between 1999 and 2009, from 15 European countries, providing 8964 measurements. Anemia was defined as having Hb levels below <11 g/dl for those over the age of 2 years and below 10.5 for those below the age of 2. All analyses were performed using linear mixed model analyses with adjustment for age, gender and cause of renal failure.

Results: Mean Hb level among renal allograft recipients was 11.9 g/dL (5th and 95th percentiles, 9.3 to 14.4). 26.8% of patients were anaemic despite the use of erythropoietin stimulating agents in 17.7%, and iron in 27.8% among all transplanted patients.

Patients who received a pre-emptive transplantation or those with pre-transplant dialysis duration of less than one year prior to transplantation had higher Hb levels. No differences were found between patients who received an organ from a living versus a deceased donor, nor between those who were on PD or HD before receiving their transplant. Hb levels were positively associated with estimated glomerular filtration rates. When mycophenolate mofetil (MMF) or sirolimus were part of the immunosuppressive treatment, Hb levels were slightly lower, but significance was borderline.

Conclusions: Anemia is present in 27% of pediatric kidney transplant recipients in Europe, and was not treated in more than 2/3 of the patients. Short pre-transplant dialysis duration and a higher graft function were associated with higher Hb levels. Since anemia may compromise physical and psychological well-being, close attention to low hemoglobin appears indicated.

PS1-THU-342

Short and long term continuous use of Cinacalcet in children on peritoneal dialysis

N. Printza* ¹, C. Ghogha¹, F. Papachristou¹

¹1st Pediatric Departement, Aristotle University, Hippokration General Hospital,Thessaloniki, Greece

Objectives and study: To evaluate the efficacy of Cinacalcet in children on peritoneal dialysis (PD) with severe secondary hyperparathyroidism (HP).

Methods: Between July 2009 and July 2010, 4 patients on PD, with severe secondary HP (PTH >900 pg/ml for at least two consecutive measurements), uncontrolled with phosphorus dietary restrictions combined with phosphate binders and analog of 1,25 vitamine D3, received Cinacalcet. Cinacalcet’s dose was titrated regarding patient’s respond, biochemistry and side effects. Over the duration of Cinacalcet other medications were prescribed to maintain optimal biochemical control.

Results: Four patients, 2 girls (patients 1 and 3) and 2 boys (patients 2 and 4), aged 3.5, 5, 12 and 13.5 years old, on PD fulfilled the above criteria for Cinacalcet initiation. Patients’ primary diseases were diarrhoea + haemolytic uremic syndrome (1), renal dysplasia (2 and 4) and steroid resistant nephrotic syndrome (3). PD duration ranged from 14–26 months. Prior to Cinacalcet initiation all patients presented normal calcium values while patients 3 and 4 presented constantly elevated phosphorus values (6.3–8 mg/dl). At the same time, PTH values (median) were 1250 pg/ml, 1350 pg/ml, 930 pg/ml and 1150 pg/ml for patients 1, 2, 3 and 4 respectively. Cinacalcet dose in mg/kg was 0.4, 0.4, 0.5–0.8 and 0.5–0.8 and the duration of treatment in months was 1, 1, 6 and 12 for patients 1, 2, 3 and 4 respectively. No major adverse effects were noticed. Episodes of hypocalcaemia were non-symptomatic. Post Cinacalcet treatment PTH values (median) were 250 pg/ml, 370 pg/ml, 950 pg/ml and 1700 pg/ml and the duration of follow up (months) were 18, 6, 12 and 15 for patients 1, 2, 3 and 4 respectively. Patients 3 and 4 underwent surgical parathyroidectomy.

Conclusions: Cinacalcet may be an effective treatment for PD patients with secondary HP. Children seem to respond soon after treatment initiation and short monthly courses may be effective. However SP can not be avoided in certain cases specially those of longstanding HP.

PS1-THU-347

Success rate and survival of arteriovenous access surgery in children; a retrospective two-centre study

N. Marien*¹, M.J.S. Oosterveld², R. Van Damme-Lombaerts¹, M.R. Lilien², N.B.B. Knops²

¹University Hospital Leuven, Campus Gasthuisberg, Leuven, Belgium, ²Wilhelmina Children’s Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands

Objectives and study: The NKF-KDOQI-guidelines recommend creation of an arteriovenous (AV) fistula (AVF) or graft (AVG) for permanent haemodialysis (HD) access. There are sparse data regarding success rates of AV access surgery in children, especially in children under the age of 6 years. We report the primary and secondary survival rates of AV access surgery in children.

Methods: We reviewed the charts of all patients starting chronic HD between April 1987 and November 2009 in two tertiary paediatric nephrology centres. Various potential determinants of surgical outcome were assessed. A subgroup analysis was performed for children under the age of 6 years.

Results: A total of 138 AV access procedures were performed in 96 patients (44 females, 45.8%). The mean (±SD) age at time of surgery was 11.9 ± 4.3 years and 18 (13%) of procedures were in children aged 6 years or less. Most patients (95.6%) received an AVF, in 6 cases an AVG was created. Fistulas were placed at the wrist in 101 (76.5%) of cases and 30 (22.7%) at the elbow (in 1 case AVF position was unknown). Primary failure rate of all AV access procedures was 26.1%. Median (range) follow up from access creation was 873 (48–5477) days, with most cases (69.6%) lost to follow up due to transplantation. In 102 functioning AV accesses, secondary failure occurred in 14.7%. Kaplan-Meier analysis revealed no statistical difference in survival when procedures were stratified by AVF position (wrist vs. elbow), pre-operative imaging of vasculature or previous ipsilateral central venous catheter placement. Finally, outcome parameters were not statistically different in children under the age of 6 years.

Conclusions: Primary failure of AV access surgery in paediatric patients is substantial. Survival analysis yielded no single determining factor of surgical outcome. Short and long term outcome is not significantly inferior in younger children.

PS1-THU-353

Fighting bloody diarrhea for HUS prevention and mitigation: lombardy regional HUS network

G. Ardissino*¹, F. Tel¹, S. Testa¹, F. Paglialonga¹, S. Salardi², N. Borsa Ghiringhelli², S. Tedeschi², R. Colombo, M. Colosimo³, E. Torresani⁴

¹Pediatric Nephrology Unit, IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy, ²Medical gentics Dept, Molecular Biology Unit, IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy, ³Laboratory of Clinical Pathology, Microbiology Unit, IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy, ⁴Laboratory of Clinical Pathology, IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy

Typical hemolytic uremic syndrome (tHUS), although rare, still represents a major public health problem in industrialized countries caused by a Verotoxin-producing Escherichia coli (VTEC) intestinal infection often presenting with bloody diarrhea. In order to identify patients at risk of tHUS early in the course of the disease, a network connecting pediatric hospitals in Lombardy Region (10 millions gp) was developed. Fifty-three units presently partecipate in the network and since May 28, 2010 (founding day) children with bloody diarrhea were centrally tested for Shigatoxin (Stx) 1 and 2 with a rapid immunochromatographic test and multiplex PCR test. The objectives of the project were: 1. to increase the ability of the surveillance system in identifying the sources of VTEC infection and its spreading; 2. to understand the mechanisms of Stx delivery to target organs endothelia; 3. to test the potential role of overhydration and/or leukoapheresis to prevent or mitigate renal and CNS involvement. So far 189 patients have been tested. Hereafter are the preliminary results concerning the 47 samples for which all the procedures were completed. Six out of 47 (12.7%) were positive for VTEC. Among negative samples Salmonella (24%) and Campylobacter (12%) were the most common identified bacteria. Among patients with negative colture (43%) 1 patient had Henoch Schonlein purpura, 1 ulcerative colitis and 1 Meckel diverticulum. In conclusion, our findings point out an unexpected very high frequency of VTEC among bloody diarrhea in children in our region. No conclusion can be anticipated on the remaining objectives.

Acknowledgement: The project is feasible thanks to the collaboration of the members of the Regional HUS Network whose complete list is available at https://doi.org/www.centroseu.org. The project has been supported by the “PROGETTO ALICE ONLUS—Associazione per la lotta alla SEU”not found to be useful in discriminating children with VUR.

PS1-THU-355

Long-term decline of GFR in children with CKD with and without growth hormone (GH) treatment: lessons from kigs and escape

O. Mehls*¹, A. Lindberg², D. Haffner³, E. Wuehl¹

¹Univ. Hospital for Chilren and Adolecents Heidelberg, Germany, ²Pfizer Endocrine Care (A.L.), KIGS/KIMS/ACROSTUDY, S-19190 Stockholm, Sweden, ³Univ. Childrens Hospital Hannover, Germany

Background: GH treatment has been suspected to result in hyperfiltration and progressive decline of renal function. Controlled long-term observations are not available.

Methods: We performed a longitudinal analysis of the decline of renal function over 5 years in 93 short children with CKD II–IV receiving GH treatment, reported to the Pfizer-KIGS database (age at start 6.2 ± 3.2 yrs; males 72%; renal hypodysplasia 59%; glomerulonephritis 8%; hereditary and others 33%). The control group consisted of 113 non-GH treated children from the ESCAPE trial, followed over a period of 5 years (age at start 10.9 ± 4.0 yrs; 62% male; hypodysplasia 77%; glomerulonephritis 10%; hereditary and others13%). In addition, a cross-sectional analysis over up to 10 years was performed for 371 KIGS patients.

Results: GFR at start was 40.7 ± 21.1 ml/min × 1.73 m² in the KIGS group, and 54.3 ± 14.9 in the ESCAPE group. Delta GFR over 5 years in KIGS was 4.9 ± 15.8 and 8.6 ± 13.2 ml/min × 1.73 m² in ESCAPE (p = 0.05) with a comparable dropout rate over 5 years in both groups. In a cross-sectional analysis of 10 years of GH treatment in the KIGS population, no acceleration of decline of renal function was noted during the second half of the decade. Delta GFR at 1 and 3 years was negatively correlated to age (r = −0.338; p < 0.01), height and weight and primary renal disorder but not to mean weekly dose/kg of GH. However, in multivariate analyses age nearly exclusively explained the variation for Delta GFR.

Conclusion: Over a period of 10 years, no negative effect of GH treatment on renal function was noted in short children with CKD.

PS1-THU-356

Safety and effectiveness of a 2009 H1N1 vaccine in chronic kidney disease children

O. Dönmez* ¹, A. Korkmaz¹, O. Akaci¹, O. Durmaz², N. Albayrak², A.B. Altaş²

¹Uludag Universty Pediatric Nephrology Department, Burza, Turkey, ²Ankara Refik Saydam Hıfzıssıhha Center, Ankara, Turkey

Background: In April 2009, the emergence of Swine Flu in humans caused the influenza pandemia.The goal of this pediatric clinical trial was to assess the safety and immunogenicity of one dose of a monovalent inactivated pandemic (H1N1) 2009 vaccine in Uludag Universty pediatric nephrology department of chronic kidney disease children.

Methods: Twenty-five children and adolescents with chronic kidney disease were received one dose of the monovalent inactivated pandemic (H1N1) 2009 vaccine. We assessed adverse events after immunization in 21 days and compared prevaccination and postvaccination hemagglutination inhibition (HI) antibody responses. Geometric mean titres were defined >4-fold increase after vaccination. In patient group, 25 children were studied, 16 of whom were treated with peritoneal dialysis, 2 of whom were treated with hemodialysis, 3 of whom were kidney transplant recipients and 4 of whom were predialysis patients. Serum of prevaccination and postvaccination were studied in terms of A/H1N1 antibodies in Refik Saydam Hıfzıssıhha Center.

Results: In study group, 25 children were studied, 13 of whom were boys.The group of mean age was 14,6 ± 3,28 years. When the pandemic vaccine was administered sequentially to the seasonal vaccine, it was significantly immunogenic in the chronic kidney disease children. İncreased hemagglutination inhibition (HI) antibody responses occured in %92 patients. Seroconversion rates and the geometric mean titres of all of the seasonal antigens were occured in the %84 patients. Simultaneous administration was associated with a better immune response against A/H1N1 antigens in chronic kidney disease patients ,and did not increase the mild local and systemic reactions. No impact on renal function was observed.

Conclusions: This study demonstrate the high level immunogenicity and safety of an (H1N1) 2009 influenza vaccine in chronic kidney disease children.

PS1-THU-358

Don’t forget body mass index when you assess dry weight using bioimpedance resistance in children on hemodialysis

M. Kostić¹, B. Spasojević-Dimitrijeva¹, A. Peco-Antic¹, M. Petrović*¹, I. Šimić², M. Cvetković¹, I. Ivanišević¹, S. Purić¹, I. Gojković¹

¹University Children’s Hospital, Belgrade, Serbia, ²Heidelberg University, Heidelberg, Germany

Objectives and study: To determine significance of bioimpedance as a noninvasive parameter for assessment of dry weight, in a relation to body mass index (BMI), and to determine the correlation between bioimpedance resistance (BIR) and hematocrit values.

Methods: 10 children on a programme of chronic hemodialysis were involved in this research. 182 measurements of BIR before and after hemodialysis were performed using Monofrequenz-Impedanz-Analysator B.I.A. 2000-C. Anthropometric measurements were performed before and after hemodialysis, BMI was calculated, and hematocrit was measured before hemodialysis. According to BMI, patients were divided into three groups (group 1—BMI ≤14.9, 2—BMI 15–19.9, 3—BMI ≥20 kg/m2). SPSS was used for the statistical analyis.

Results: BIR before hemodialysis is in a positive correlation with hematocrit. BIR before and after hemodialysis is in a negative correlation with BMI before and after hemodialysis. Average changes of BIR before and after hemodialysis (ΔR) were: 163.26 ± 74.39 in group 1, 150.7 ± 75.79 in group 2, 95.67 ± 48.1 in group 3. We noticed that ΔR is considerably higher in group 1 compared to group 3, but that difference doesn’t reach statistical significnace. BIR values after hemodialysis (group 1 = 1007.46 ± 129.16, group 2 = 842.24 ± 116.23, group 3 = 570.17 ± 88.66) are statistically significantly different between the three groups. Values of BIR after hemodialysis show highly significant statistical difference between the subgroups formed on the basis of reduction of body weight (ΔBW) after hemodialysis (subgroup 1—ΔBW<1 kg, 2—ΔBW 1–2 kg, 3—ΔBW >2 kg) within the first two groups and statistical significance in the third group.

Conclusion: BMI has a significant influence on the BIR values, and when assessing dry weight in children on hemodialysis one can interpret values of BIR only while taking BMI into consideration.

PS1-THU-359

Mesenchymal stem cells and antioxidant system in chronic peritoneal dialysis model

M.H. Poyrazoğlu*¹, S. Tülpar¹, Z. Gündüz¹, F. Baştuğ¹, H. Özbilge², E. Çetin³, Y.A. Torun⁴, H. Akgün⁵, E.G. Kaya², R. Düşünsel¹

¹Department of Pediatric Nephrology, Erciyes University Faculty of Medicine, Kayseri, Turkey, ²Department of Pharmaceutical Microbiology, Erciyes University Faculty of Pharmacy, Kayseri, Turkey, ³Department of Physiology, Erciyes University Faculty of Veterinary Medicine, Kayseri, Turkey, ⁴Kayseri Education and Research Hospital, Kayseri, Turkey, ⁵Department of Pathology, Erciyes University Faculty of Medicine, Kayseri, Turkey

Objective: The aim of the present study was to investigate the effect of mesenchymal stem cells (MSC) transplantation on the peritoneal morphology and antioxidant system in rat models of chronic peritoneal dialysis (PD).

Material-methods: Wistar albino male rats were divided into four groups: Control (C) group, Peritoneal dialysis (PD) group, MSC group and placebo (P) group. PD, MSC and placebo groups received daily intraperitoneal injection with 3.86% glucose-based PD fluid once daily during six weeks. After 6 weeks, MSC group was treated with MSC and placebo group was treated with phosphate buffer solution via intraperitoneal injection. Rats without dialysis and treatment served as controls. Placebo and MSC groups were evaluated at the second and third week of treatment (MSC2, P2, MSC3 and P3 groups). At the end of the study, parietal peritoneum sample was taken from all rats under anesthesia. The activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in the peritoneal tissue were studied by ELISA method. The submesothelial thickness was measured.

Results: The submesothelial area was significantly thickened in PD and placebo groups compared with C and MSC groups. Levels of GPx and SOD were significantly increased in the PD group compared to the C group. At second week, the levels of GPx and SOD in MSC group were lower than PD group while the level of SOD in MSC group was higher than P group. At third week, GPx and SOD levels in MSC and P groups were significantly lower than PD group.

Conclusions: In our study, MSC markedly decrease submesothelial thickness. The beneficial effect of MSC on the peritoneum may be partly through antioxidant system. Mesenchymal stem cells may offer promise as novel therapeutics in peritoneal dialysis patients to protect the peritoneal membrane.

PS1-THU-369

Renal involvement in infantile panniculitis with uveitis and systemic granulomatosis

S. Krid*¹, O. Boyer¹, P. Krug-Tricot¹, C. Wouters², P. Quartier², B. Bader-Meunier², P. Niaudet¹, R. Salomon¹

¹Pediatric Nephrology, Hôpital Necker-Enfants Malades, Paris, France, ²Immuno-hematology, Hôpital Necker-Enfants Malades, Paris, France

Infantile Panniculitis with Uveitis and Systemic Granulomatosis (IPUSG) is a rare condition characterized by febrile lobular panniculitis associated with arthritis, uveitis, and widespread granulomatous inflammation.

We report the first case of interstitial granulomatous nephritis in a patient with this disease. A 10 year-old girl was referred to our Department for acute kidney injury. Her medical history was remarkable for diagnosis and treatment of IPUSG since the age of 4 months. She had presented numerous systemic flares which associated fever, lobular panniculitis, polyadenomegaly, polyarthritis, uveitis, intersitial pneumonitis, aseptic meningitis, hemolytic anemia and inflammatory syndrome. Multiple granulomas composed of non-caseating epithelioid cells were found in the synovial, dermal and lung biopsy samples. No CARD15 mutation involved in early-onset sarcoidosis and Blau syndrome was identified. Various treatments including NSAIDs, prednisone, ciclosporin and colchicin failed to induce remission. The introduction of anti-TNF monoclonal antibody (Infliximab) allowed a better disease control. At the age of 6 years, she presented hypercalcemia (3.13 mmol/L) and hypercalciuria and nephrocalcinosis. At 10 years-old, during a systemic flare, under prednisone/infliximab/methotrexate, she presented acute renal failure (eGFR = 59 ml/min/1.73 m²) with macroscopic hematuria and proteinuria (1.3 g/L). The kidney biopsy showed interstitial infiltration with inflammatory cells and interstitial non-caseating epithelioid granulomas, severe tubular epithelial necrosis and several sclerosed glomeruli. Three methylprednisolone pulses and an increased dose of prednisone from 7 to 20 mg/d led to a quick normalization of renal function. However, macroscopic hematuria and proteinuria persisted and mycophenolate mofetil was introduced two months later. Four months later, the child was afebrile, urine was clear and proteinuria had decreased to 0.35 g/L.

This case suggests that granulomatous nephritis may occur in children with IPUSG. Therefore, a careful renal follow-up is mandatory in such patients.

PS1-THU-371

Nesfatin-1 ameliorates sepsis-induced cerebral and renal damage: the role of oxidant-antioxidant status and neutrophils

Z.N. Ozdemir*¹, A. Cumhur², A.I. Oluk², A. Hoscan², I. Onem², G. Contuk³, F. Ercan³, B. Yegen¹

¹Marmara University School of Medicine Department of Physiology, Istanbul, Turkey, ²Marmara University School of Medicine Student, Instanbul, Turkey, ³Marmara University School of Medicine Department of Histology & Embryology, Istanbul, Turkey

Acute kidney failure is a common clinical problem in neonatal intensive care units and is usually associated with sepsis. Nesfatin-1 with anorexigenic and anxiogenic properties was identified in the adipose tissue, gastric mucosa, pancreatic beta-cells and in several brain areas. It was shown that neurons expressing nesfatin-1 in the brainstem and hypothalamus have a potential role in the complex neuronal circuitry as a coordinated response to infection or inflammation. In the present study, we aimed to investigate the possible protective effects of intraperitoneal (i.p.) nesfatin-1 against oxidative organ injury in a rat model of sepsis. Under ketamine anesthesia (100 mg/kg; i.p.) sepsis was induced by cecal ligation and perforation method. Male Sprague-Dawley rats (n = 24) were divided into sham-operated control, saline-treated sepsis and nesfatin-1 (10 μg/kg; i.p.) -treated sepsis groups. The rats were killed 16 h after the operation. Kidney and brain samples were obtained for histological analysis and for the measurement of myeloperoxidase (MPO) activity and malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. Values are means ± S.E.M. compared by ANOVA. Compared to control groups, in saline-treated rats sepsis resulted in significant decreases in GSH, SOD and CAT levels with significant increases in MDA levels and MPO activity (p < 0.05−0.001), showing oxidative damage in both kidney and brain tissues. On the other hand, treatment with nesfatin-1 alleviated sepsis-induced tissue damage, while MDA level and MPO activity were reduced along with the preservation of the antioxidant GSH, CAT and SOD levels in both tissues (p < 0.05). These results support the anti-inflammatory and protective effects of nesfatin-1 in sepsis-induced oxidative damage by maintaining a balance in oxidant-antioxidant status through the augmentation of endogenous antioxidants and the inhibition of neutrophil recruitment.

PS1-THU-374

Combined hemodialysis and plasma exchange versus sequential treatment in children

B. Schaefer*¹, R. Goldwasser¹, S. Schaefer¹, K.H. Heckert¹, F. Schaefer¹, C.P. Schmitt¹

¹Center for Pediatric and Adolescent Medicine, University of Heidelberg, Division of Pediatric Nephrology, Heideberg, Germany

Background: Patients with immune-mediated kidney disease and liver failure often require plasma exchange (PE) and hemodialysis (HD). Combining both methods, i. e. connecting the PE and HD circuit in series, should allow for a more efficient treatment. The outcome has not yet been evaluated.

Methods: 15 out of 45 children (7.8–38.5 kg) were treated with combined (c) PE/HD, eight alternately with both c and sequential (s) PE/HD (12.4–80.9 kg), and 22 (5–75 kg) with sPE/HD only. Treatment modalities, efficacy, anticoagulation and clinical findings were analyzed retrospectively.

Results: Mean treatment duration was 3.9 ± 2.3 h per session for cPE/HD and 5.9 ± 1.7 h with sequential therapy (HD 3.8 ± 2.3 h, PE 3.7 ± 1.6 h; p < 0.001). Dialysate flow was 509 ± 187 with cPE/HD and 331 ± 171 ml/min/m² with sPE/HD (p < 0.01). PE/HD filter size per m² and blood flow rates were similar (cPE/HD 113 ± 45, sPE 92 ± 23, sHD 111 ± 28 ml/min/m²; all p = n.s.). Initial bolus of heparin consisted of 999 ± 729 for cPE/HD, 389 ± 475 for sPE and 305 ± 457 IU/m² for sHD (p = n.s. for cumulative dose). The dose of continuous and total heparin infusion and Activated Clotting Time were similar, as was the cumulative amount of citrate and calcium chloride infused in children treated with either method (n = 15). Dialysis efficacy (creatinine, phosphate, urea and bilirubin removal) and ultrafiltration rates were comparable (cPE/HD 835 ± 660 vs. sPE/HD 936 ± 535 ml/m², p = n.s.). Both methods were well tolerated. Blood leakage and hemolysis occurred in 8/83 cPE/HD sessions (10%) and in 3/107 sPE/HD sessions (3%), hypothermia in one sPE/HD session (1%).

Conclusions: PE/HD performed in series within one session is safe and allows for a more rapid purification as compared to sequential therapy. This is of particular interest in patients with severe diseases. Careful dialysator pressure control, however, is required to prevent hemolysis and capillary leaks.

PS1-THU-375

Kidney transplantation in patients with body weight less then 20 kilograms—single centre experience

S. Puric*¹, M. Kostic¹, B. Spasojevic-Dimitrijeva¹, A. Peco-Antić¹, Z. Krstic¹, G. Milosevski-Lomic¹, D. Paripovic¹, M. Cvetkovic¹

¹University Children’s Hospital, Belgrade, Serbia

Objectives and study: Age of children at the time of kidney transplantation strongly influences the outcome. Aim was to present five years patient’s and graft survival rate in respect of body weight at the time of transplantation.

Methods: Group of 43 children transplanted at the University Children’s Hospital between years 2001–2010 was analyzed. Patients were grouped according to their body weight at the time of transplantation in group A—children with body weight (BW) below 20 kilograms and group B—children with BW over 20 kilograms.

Results: Mean age of patients was 12.64 ± 4.79. Ten patients (23%) had body weight less then 20 kilograms. Average age and BW in group A was 5 years 8 months and 15.6 kg respectively, while in group B it was 14 years 6 months, and 35 kg respectively. Most common underlying diseases in group A were glomerular disease and nephronophtisis, while in group B it was congenital anomalies of kidney and urinary tract (CAKUT). There were no differences in average waiting time, graft origin and induction therapy between two groups. Average follow-up period was 4 years 2 months and 3 years 5 months in group A and B respectively. Overall cumulative patient’s survival rate was 96% after five years. Five years cumulative graft survival rate in group A was 90% and 76% in group B. Graft function (77 ml/min/1.73 m² vs. 63 ml/min/1.73 m²) was significantly better in group A.

Discussion: Better outcome in patients with lower body weight during the follow-up was a result of poor compliance in group B.

KEY WORDS: kidney transplantation, low body weight, outcome.

PS1-THU-379

Clinical experience of everolimus in pediatric renal transplant recipients

N. Dincel*¹, O.D. Kara¹, A. Keskinoğlu¹, S. Şen¹, C. Hoşcoşkun¹, C. Kabasakal¹, S. Mir¹

¹Ege University Medical Faculty, Izmir, Turkey

Everolimus is a proliferative signal inhibitor(PSI) that blocks growth factor dependent T-cell proliferation,can regress calcineurin inhibitor(CNI) toxicity without decreasing its own immunsupressive effect.The use of PSI regimens may reduce the rate of chronic vascular disease and allograft nephropathy(CAN).Our aim is to report our experience with everolimus conversation among patients with CAN and CNI toxicity.

We analyzed outcomes of 18 patients undergone transplantation and conversion of therapy from a calcineurin inhibitor to everolimus because of biopsy-proven CAN(n = 10), CNI toxicity(n = 5),presence of malignancy(1 lymphoproliferative disease,2 fibroadenomas).Acute rejection, transplant glomerulopathies and C4d (+) states were ruled out by biopsy. Patients having CAN findings in their biopsy were classified according to Banff score.Patients having CNI toxicity , were followed by algoritm as firstly, PRA and DSA,secondly proteinuria were controlled.At the third step, we lowered the CNI doses. If patient wasn’t responded to all, then we switched to PSI. Conversion was abrupt , well-tolerated, and safe using an initial dose of0.5-1 mg/d that was sufficient to achieve the recommended levels of 6–8 ng/dL. All patients also received steroids with mycophenolate mofetil or azathioprin.In none patients ,we used everolimus together with low dose CNI.

The mean duration of follow up was 38 +/− 5 months . The prior treatment consisted of a calcineurin inhibitor, prednisolone,azatiopyrine and mycophenolate mofetil. There were 10 patiens having CAN in their biopsy (6 biopsy were in Banff score1, 3 were in score 2 and 1 were in Banff score 3).After conversion, the calcineurin inhibitor was stopped and everolimus was begun. Each patient underwent physical examination , growth assessment (lenght development) and estimation of renal functional tests,complete blood count , serum lipid and electrolyte levels ,as well as proteinuria, monthly. Patients showed a fall in serum creatinine level to 0.5 +/− 0.09 and creatinine clearance increasing from 59.4+/−11.4 to 67+/−10.3 ml/min. Only 1 patient showed increase in proteinuria in the first 6 months of switch and proteinuria was well controlled with angiotensin-converting enzyme. After conversion, serum cholesterol levels increased from 167 +/− 12 to 198 +/− 23 mg/dL, and serum triglyceride levels increased from 145 +/−37 to 187 +/− 65 mg/dL. All patients responded to statin therapy.One patient developed unilateral lower extremity edema , one had lymphocele.

Two patients lost their grafts ,one lost was due to the patient incoordination, in other patient, although GFR was below 20 ml/min./1.73 m² at the time of switch ,by switch graft lost was delayed 5 years. CNI toxicity can lead to graft loss, itshelf directly or indirectly by leading to chronic allograft nephropathy. In our experience, conversion to everolimus was associated with improved renal function among patients with chronic allograft nephropathy or CNI toxicity, even in patients with significantly decreased renal function at the time of the switch.Everolimus displayed a limited incidence of adverse effects easily controlled with countermeasure therapy.

PS1-THU-383

Prevalence and significance of donor specific antibodies in paediatric kidney transplantation

D. Athavale*¹, J. Worthington², D. Roberts¹, N. Webb¹, M. Shenoy¹

¹Department of Paediatric Nephrology, Royal Manchester Children’s Hospital, Manchester, UK, ²Renal Transplantation Unit, Manchester Royal Infirmary, Manchester, UK

Objectives and study: Antibody mediated rejection (AMR) is increasingly recognised as a cause of graft dysfunction and subsequent graft loss. However, the prevalence in paediatric kidney transplant (KT) population is unknown and correlation with graft dysfunction and response of donor specific antibodies (DSA) to treatment remains unclear. We studied the prevalence of DSA in our paediatric KT population and analysed correlation with graft dysfunction and response to changes to immunosuppressive therapy.

Methods: All patients attending our transplant clinic were tested for DSA, measured using microbead array technology, irrespective of graft function. Any patient having a positive result subsequently underwent historic testing on samples sent previously. Patients with graft dysfunction underwent a renal biopsy; C4d staining was performed on all specimens. In those patients where AMR was diagnosed, DSA titres and eGFR were monitored following changes in immunosuppressive regime.

Results: Eight of a total of 53 patients (15.1%) were DSA positive with graft dysfunction present in five patients. Four of these patients had biopsy changes consistent with acute cellular rejection (Banff 1a-1b) and one had chronic transplant glomerulopathy with C4d staining positive in four. Non-adherence to immunosuppressive therapy was an issue in four of these five patients. Graft function stabilised in four following pulse methylprednisolone and intensification of background immunosuppression. One patient, who developed severe rejection and was dialysis dependent received immunoglobulins and rituximab which resulted in improvement both in eGFR and DSA levels. Three patients are DSA positive with no evidence of graft dysfunction 2.7 to 11.3 years following transplantation.

Conclusions: DSA are present in a significant number of our KT recipients. Treatment of acute rejection with steroids and intensified background immunosuppression appears to reduce DSA levels and stabilise graft dysfunction. The significance of DSA in patients with stable graft function remains unclear.

PS1-THU-385

Obesity: an independent risk factor for hypertension, decreased GFR and chronic renal disease

A. Duzova*¹, O. Soylemezoglu², F. Yalcinkaya³

¹Hacettepe University Faculty of Medicine, Pediatric Nephrology and Rheumatology Unit, ²Gazi University Faculty of Medicine, Dept. of Pediatric Nephrology, Ankara, ³Ankara University School of Medicine, Dept. of Pediatric Nephrology, Ankara

Objective: To assess the effect of obesity on hypertension, glomerular filtration rate (GFR) and chronic renal disease (CRD) among children in a field study.

Methods: A population-based field study in which individuals were accessed by house visits throughout Turkey has been conducted. The study sample (3074 children) was selected to represent Turkish population regarding to geographical region, gender and age (5 to 18 years). Obesity was defined as body mass index ≥95th percentile for age and gender. Schwartz formula was used to estimate GFR. Blood pressure (BP) percentile was determined according to age, gender and length. CRD was defined as presence of GFR <75 ml/min/1.73 m² and/or blood pressure ≥99th percentile and/or proteinuria.

Results: The prevalence of obesity, hypertension (≥95th percentile), low GFR (<90 ml/min/1.73 m²) were 3.8%, 3.9% and 3.0%, respectively. GFR was <75 ml/min/1.73 m² in 0.7%; and BP was ≥99th percentile in 1.6% of the study group. The prevalence of CRD was 5.1%. Obesity increased risk for BP ≥95th percentile (OR 4.67, 95%CI 2.65–8.22; p < 0.001), BP ≥99th percentile (OR 6.37, 95%CI 3.01–13.49; p < 0.001), GFR <90 ml/min/1.73 m² (OR 3.28, 95%CI 1.65–6.50; p < 0.005), GFR <75 ml/min/1.73 m² (OR 4.07, 95%CI 1.19–13.95; p < 0.05), and chronic renal disease (OR 3.76, 95%CI 2.06–6.85; p < 0.001). Logistic regression analysis revealed obesity to be the most significant independent risk factor for the aforementioned parameters.

Conclusion: This population-based field study showed that the prevalence of hypertension, low GFR and CRD is noteworthy in Turkey; strategies for the prevention and management of obesity which was the major independent risk factor are crucial.

The Study was supported by TUBITAK (The Scientific and Technological Research Council of Turkey)

PS1-THU-386

Role of urine kidney injury molecule-1 as an early marker of acute renal failure in newborns with respiratory distress syndrome

G. Genc*¹, O. Ozkaya¹, B. Avci², C. Aygun³, S. Kucukoduk³

¹Ondokuz Mayis University Medical Faculty, Department of Pediatric Nephrology, Samsun, Turkey, ²Ondokuz Mayis University Medical Faculty, Department of Biochemistry, Samsun, Turkey, ³Ondokuz Mayis University Medical Faculty, Department of Neonatology, Samsun, Turkey

Objectives and study: To evaluate the role of Kim- 1 in early determination of renal injury in prematures with respiratory distress syndrome (RDS).

Methods: Forty eight premature hospitalized in Ondokuz Mayis University Faculty of Medicine Neonatal Intensive Care Unit were included in the study. Patients were divided into 3 groups; Group I: Healthy premature babies, Group II: Patients with Respiratory distress syndrome (RDS) but without renal failure, Group III: Patients with RDS and renal failure. Clinical and laboratory features of the patients and postnatal complications were recorded. Urine Kim-1 and blood creatinine levels were measured with ELISA on 1st, 3rd and 7th days.

Results: No correlation was found between Kim-1 levels and gestational age, birth weight, scores for Clinical risk index for babies and hypotension. Kim-1 levels in patients with RDS on 1st day were higher than healthy premature newborns (p = 0.008). An increase in creatinine levels on 3rd day was detected in patients who had RDS and high Kim-1 levels on 1st day (r = 0.388, p = 0.016). The increase in Kim-1 levels on 3rd day relative to 1st day had been shown to have predictive value in indicating renal failure. The sensitivity and specificity of Kim-1 were found to be 73.3% and 76.9% respectively when there was an increase of 5 ng/ml/mg creatinine in 3rd day compared to 1st day.

Conclusions: Monitoring urine Kim-1 levels can be a parameter which can be used for early diagnosis and follow up of renal failure in premature newborns with RDS. Postnatal daily urinary monitoring of Kim-1 levels may guide the evaluation of renal damage, fluid therapy, nonsteroidal anti-inflammatory drug management and nephrotoxic drug dosages like aminoglycosides in these patients.

PS1-THU-388

A twenty-two year epidemiological surveillance of pediatric aemolytic uremic syndrome in Italy

G. Scavia*¹, A. Edefonti², E. Vidal³, F. Emma⁴, C. Percoraro⁵, A. Amore⁶, A. Caprioli¹, E. Verrina⁷

¹Istituto Superiore di Sanit, Rome, Italy, ²Clinica Pediatrica G. e D. De Marchi, Milan, Italy, ³Azienda Ospedaliera di Padova, Padua, Italy, ⁴Ospedale Bambino Gesù, Rome, Italy, ⁵Ospedale Santobono Pausilipon, Naples, Italy, ⁶Ospedale Infantile Regina Margherita, Turin, Italy, ⁷IRCCS G. Gaslini, Genova, Italy

Hemolytic Uremic Syndrome (HUS) is a common cause of acute renal failure in children. In Italy, a National Registry of HUS in children was established since 1988 by the Italian Pediatric Nephrology Society, in cooperation with the National Reference Laboratory for E. coli. The main aim was to carry out surveillance of HUS, to estimate the burden of the disease in the population and to monitor the associated infection due to Verocytotoxin (VT)-producing E. coli (VTEC).

Laboratory diagnosis of VTEC infection is based on the isolation of VTEC strains, the detection of free VT in stools and the detection of serum antibodies to the lipopolysaccharide (LPS) of the most important serogroups.

Up to December 2010, 723 cases of HUS have been identified, accounting for a mean annual incidence of 0.38 × 10−5. Most of the patients reported prodromal watery (36%) or bloody (47%) diarrhoea. Evidence of VTEC infection was observed in 73% of the 647 cases examined. The serogroups detected most frequently were O157 (35%), O26 (26%), O145 (12%), O111 (10%) and O103 (5%). Cases associated with non-O157 infections have increased over time, and since 1998 they outnumbered those due to O157. Non-O157 serogroups prevailed also in the etiology of the outbreaks detected during the study period. VTEC O26 was associated with 4 outbreaks while O111, O55 and O157 with one. Other differences between VTEC serogroups involved the age of patients (median: 32 months for O157; 22 for non-O157) and the seasonality, with a more clear summer pattern for VTEC O157.

Surveillance data suggest that the incidence of HUS in Italy is rather low if compared with that of other industrialized countries and that the role of non-O157 serogroups in the etiology of HUS can not be overlooked. This highlights the need for a comprehensive laboratory approach to the diagnosis of VTEC infection.

PS1-THU-395

Growth and the need of growth hormone therapy in children with chronic kidney disease are associated with birth parameters and parental height

M. Živičnjak* ¹, H. Alakan¹, L. Pavičić², J.H.H. Ehrich¹, L. Pape¹, J. Grohe¹, C. Rudomski¹, U. Querfeld³, D. Müller³, D. Franke³

¹Department of Paediatric Kidney, Liver and Metabolic Diseases, Children’s Hospital, Hannover Medical School, Hannover, Germany, ²Faculty of Kinesiology, University of Zagreb, Zagreb, Croatia ³Department of Paediatric Nephrology, Charité University Hospital, Berlin, Germany

Background: Poor growth is a clinical hallmark in children with chronic kidney disease (CKD). We analysed if parental height and birth history may be predictors for growth failure and the need for growth hormone (GH) treatment.

Methods: Four hundred ninety-two children with CKD stage 3–5 were divided into a group with good growth (GG, no history of GH therapy, height >−2 SDS, 227 children) and a group with poor growth (PG), which consisted of 192 children with GH treatment and 73 with a height SDS <−2 and no GH treatment. The impact of parental height and birth data (gestational age, birth weight, length, head circumference, umbilical cord pH, APGAR scores) on GH requirement was evaluated with binary logistic regression analysis.

Results: The rate of pre-term children (<37 weeks) in the GG group was 26% compared to more than 42% in PG group (p < 0.001). Out of a total of 110 small-for-gestational-age patients, 80.9% were in the PG group (p < 0.001). Median birth weight in newborns with GG was more than 400 gr higher and birth length 2 cm longer than in newborns with PG (p < 0.001 each). Children with GG had on average 4 cm taller parents (p < 0.001) and higher gestational ages and APGAR scores (p < 0.05) than children with PG.

Binary logistic regression analysis demonstrated that parental height and birth data explained 32.5% of variance of group membership (PG versus GG), capable for statistically significant prediction of 70.8% overall group membership (GG 67.2% and PG 73.8%).

Conclusions: Intrauterine growth retardation, prematurity and parental height had a significant impact on postnatal growth in children with CKD. Therapeutic decisions such as alimentation strategies, early initiation of growth hormone treatment and prediction models should take perinatal parameters into account in order to further improve postnatal growth.

PS1-THU-398

Three-dimensional ultrasonographic determination of the functional renal volume in paediatric renal grafts and correlation with renal graft function

D. Franke*¹, S. Haase¹, L. Pape¹, M. Živičnjak¹

¹Paediatric Nephrology, Hannover Medical School, Hannover, Germany

Purpose: The transplanted renal mass has an impact on renal function. The 2D estimation of the renal volume using the ellipsoid formula is known to underestimate the real volume. Therefore, we calculated the total and the functional renal volume using 3D ultrasonography and related it to renal function.

Patients and methods: From September 2007–April 2011, 74 children and adolescents with renal transplantation were examined at Hannover Medical School (48 boys, 26 girls) with the Toshiba Aplio XG and the 5 MHz PVT 575MV probe by a single investigator. Mean age at renal transplantation was 10,8 years (1,4–17,9 years). For each child 3–5 measurements were obtained and the renal volume was calculated using the ellipsoid formula and the 3D volumetry both for the total renal volume and the volume of the renal pelvis. The functional renal volume was evaluated by substracting the 3D renal pelvis from the total 3D renal volume. Glomerular filtration rate (GFR) was derived from serum creatinine values determined at the time of ultrasonography by using the Schwartz formula.

Results: Mean 3D total renal graft volume was 181,8 ± 62 ml and differed significantly (p < 0,01) from mean 2D volume (137,4 ml). The mean functional volume was 158,1 ml. We analysed three groups of children: <1 year after RTx. 1–5 years and >5 years after RTx. The total and the functional volume was lower in children with a longer duration after RTx. Mean GFR decreased from 77 to 68 to 47 ml/1.73 m² in the three groups, p = 0,002.

Conclusion: The 3D ultrasonographic determination of renal graft volume is a fast, noninvasive and time-effective tool for determination of the functional renal volume, which correlates with renal function.

PS1-THU-401

Late recovery of renal function by rituximab in a patient with Wegener granulomatosis

M. Malina*^1,2, F. Schaefer¹, R. Waldherr³, E. Wühl1, C.P. Schmitt¹

¹Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany, ²Pediatric dpt., Charles University in Prague—2nd Faculty of Medicine, Czech Republic, ³Gemeinschaftspraxis für Pathologie, Heidelberg, Germany

Background: In Wegener granulomatosis, an ANCA-associated vasculitis of small- to medium-sized arteries, the anti-CD20 monoclonal antibody rituximab was recently found equally effective as standard immunosuppressive protocols using cyclophosphamide and glucocorticoids.

Case: We report on a girl who developed Wegener granulomatosis with necrotizing pauciimmune glomerulonephritis at age 16.5 years. She rapidly progressed to end stage renal disease (ESRD) despite intense therapy with steroid pulses, cyclophosphamide and plasmapheresis. A follow-up biopsy after two months of treatment showed 37 out of 40 glomeruli completely sclerosed and marked interstitial fibrosis. GFR at that time was 3–6 ml/min/1.73 m² and chronic peritoneal dialysis (PD) was started. Subsequently she developed several clinical relapses associated with serological flares while on maintenance MMF/azathioprin, necessitating extended high-dose steroid therapy which led to severe Cushingoid appearance, osteopenia and femoral head necroses. In an attempt to interrupt the disease process, a single dose of rituximab (375 mg/m²) was administered two years after first manifestation. Serological and clinical remission was rapidly achieved. Moreover, over the subsequent six months we observed a steady increase in residual GFR. PD was gradually weaned and eventually discontinued. Today, 14 months after rituximab and 8 months after cessation of dialysis, she maintains a stable GFR between 20–25 ml/min/1.73 m² on a low maintenance dose of prednisone and azathioprin.

Conclusion: Rituximab is a new efficient and safe treatment for severe ANCA-associated vasculitis. Our case demonstrates a remarkable potential of kidneys to recover from damage induced by Wegener granulomatosis even in advanced disease stage when persistent remission is achieved by anti-CD20 therapy. A treatment trial with rituximab may be indicated in patients with incompletely controlled disease even when ESRD has already occurred.

PS1-THU-402

Posttransplant malignancy and sirolimus

B. Gülhan*¹, A. Düzova¹, B. Talim², B. Yalçın³, B. Koçak⁴, S. Özen¹, N. Beşbaş

¹Hacettepe University, Faculty of Medicine, Pediatric Nephrology & Rheumatology Unit, Ankara, Turkey, ²Hacettepe University, Pediatric Pathology Unit, Ankara, Turkey, ³Hacettepe University, Pediatric Oncology Unit, Ankara, Turkey, ⁴Memorial Sisli Hospital, Istanbul, Turkey

Objectives and study: Posttransplant lymphoproliferative disease (PTLD) is a life-threatening complication of renal transplantation. We report a child with PTLD who responded to reduction of immunosuppressive agents and sirolimus treatment.

Case: A three-year old child developed end stage kidney disease secondary to posterior urethral valve. Preemptive renal transplantation from living related donor was performed; the patient received basiliximab for induction therapy and prednisolone, tacrolimus, and mycophenolate mofetil (MMF) as maintenance therapy. Seven month after transplantation, gancyclovir therapy was introduced because of fever and positive plasma PCR for CMV; within few weeks he suffered from cough and dyspnea and thorax computerized tomography (CT) revealed nodular lesions suggestive for fungal infection; caspofungin, voriconazole and amphotericin B were initiated. On follow-up, mobile and painless cervical lymph nodes were noticed. Excisional biopsy revealed “monomorphic large B-cell lymphoma”; blasts were positive for CD20 and EBV antigens. There were no bone marrow and abdominal infiltration. Patient was diagnosed as “Grade I” lymphoma. Tacrolimus and MMF treatment was stopped; sirolimus treatment was initiated in conjunction with prednisolone. Cervical lymphadenopathy disappeared; assessment with positron emission tomography and a repeat thorax CT showed remission. The patient was stable (creatinine levels 0.50–0.55 mg/dl) on fourth month after diagnosis of PTLD.

Conclusion: In addition to common and well-known complications of renal transplantation, PTLD should be kept in mind. Early diagnosis and appropriate management is vital; reduction of immunosuppressive agents and sirolimus treatment provided graft and patient survival.

PS1-THU-405

Investigating FGF23 levels and its relationship with declining renal function in paediatric patients with pre-dialysis CKD stage 3–5

M. Sinha*¹, C. Turner², R.N. Dalton², P. Rasmussen¹, S. Waller¹, C.J. Booth¹, D.J.A. Goldsmith³

¹Department of Paediatric Nephrology, Evelina Children’s Hospital, London, UK, ²WellChild Laboratory, Evelina Children’s Hospital, London, UK, ³Department of Nephrology, Guy’s and St Thomas’s NHS Foundation Trust, London, UK

To investigate (i) the prevalence of elevated FGF23 and (ii) any relationship between FGF23 levels and degree of renal dysfunction in paediatric patients with pre-dialysis CKD stages 3–5. Design: Single centre prospective observational study. 71 children with pre-dialysis CKD, (CKD 3 n = 34; CKD 4 n = 25; CKD 5 n = 12), aged 11.9 ± 3.1 years, of whom 43 (60.6%) were male. 58 (81.7%) had a congenital nephropathy or dysplasia.. FGF23 levels were measured at clinic visit in addition to anthropometry and routine laboratory investigations including serum creatinine, albumin, calcium, phosphorus and intact parathyroid hormone. Results: 14 (19.7%) patients had normal FGF23 levels defined as <50 ng/L. FGF23 [median, (IQR)] levels were 78.7 (55.6, 137.6) ng/L and following log transformation normalised data with log FGF23 (mean ± sd) values of 1.96 ± 0.4 ng/L. Log FGF23 levels negatively correlated with eGFR (r = −0.48, p < 0.0001), positively correlated with serum phosphate (r = 0.25, p = 0.03) and percent fractional excretion of phosphate (r = 0.43, p = 0.01) and not with log iPTH (p = 0.22). Log FGF23 levels were higher in 48 patients on vitamin D than the 23 patients on no vitamin D (2.04 ± 0.43 versus 1.80 ± 0.26 respectively; p = 0.005). FGF levels increased significantly from CKD stages 3 to 5 (p < 0.0001) and was associated with significant increase in percent fractional excretion of phosphate from CKD 3 to 5 (0.0009). There was no significant difference in serum phosphate (p = 0.35) or serum log iPTH levels (p = 0.12) between CKD 3, 4 & 5. Conclusion: In this largest and only report in children with pre-dialysis CKD despite all children having excellent serum phosphate control, 35 (49.3%) had elevated PTH (>65 ng/l) and 57(79.3%) had elevated FGF-23 levels associated with increased phosphaturia. These observations show that counter-regulatory phosphate-reducing mechanisms in children with CKD are very active even with modest kidney functional loss.

PS1-THU-406

A rare cause of acute kidney failure in a young child; bilateral nephrolithiasis

H. Nalcacioglu¹, E. Ozden², G. Genc*¹, S. Ozsevik³, R. Sancak⁴, O. Ozkaya¹

¹Ondokuz Mayis University Faculty of Medicine Pediatric Nephology Department, Samsun, Turkey, ²Ondokuz Mayıs University Faculty of Medicine Urology Department, Samsun, Turkey, ³Ondokuz Mayıs University Faculty of Medicine Department of Pediatrics, Samsun, Turkey, ⁴Ondokuz Mayıs University Faculty of Medicine Pediatric Allergy Department, Samsun, Turkey

Introduction: Bilateral Nephrolithiasis is a rare cause of postrenal kidney failure in early childhood. In this report whe presented a 2-year-old child who was admitted to the hospital because of anuria.

Case: A 2-year-old female patient, was admitted to the hospital with the complaint of anuria. Her physical examination was normal. Her laboratory findings revealed Hemoglobin: 9.3 g/dl, Leukocytes: 10.600 /mm³, platelets: 484.000/ mm³, BUN:74 mg/dl, Creatinine: 6.8 mg/dl, Na: 130 meq/L, K: 6.5 meq/L, ph:7.22 HCO3: 7.7 mmol/l, BE −18. In the plain radiography scan, bilateral opacities were detected. Renal ultrasonography revealed bilateral hydronephrosis with dilatation of the pelvicaliceal system. A stone in a diameter of 29 mm was seen in the right renal pelvis and an other stone in a diameter of 27 mm was seen in the left ureteropelvic junction. Bilateral DJ-catheters was replaced and the kidney functions improved by the second day. Laparoscopic left nefrolitotomy was permorfed at the follow-up.

Conclusion: Bilateral nephrolithiasis should be kept in mind even in young children as a cause of acute renal failure. Early detection and rapid intervention will prevent the complications of acute renal failure and nephrolithiasis.

PS1-THU-411

Hypertension after renal transplantation in children

B. Gülhan¹, D. Ö. Hacıhamdioğlu¹, Y. Bilginer¹, F. Özaltın¹, T. Aki², A. Düzova¹, S. Özen¹, N. Beşbaş¹, R. Topaloğlu*¹

¹Hacettepe University, Faculty of Medicine, Pediatric Nephrology & Rheumatology Unit, Ankara, Turkey, ²Hacettepe University, Faculty of Medicine, Department of Urology, Ankara, Turkey

Objectives and study: Hypertension is a common problem both in adult and pediatric kidney transplant recipients. It is an important risk factor for cardiovascular morbidity and mortality in renal transplant patients. In this study, we investigated the prevalence of posttransplant hypertension in pediatric allograft recipients.

Methods: There were 33 patients that actively followed in kidney transplantation unit. Retrospective study of these patients was performed. Data regarding chronic kidney disease etiology, growth, medications, dosage and serum levels of immunosupressive medications, serum creatinine levels at first month after transplantation, number of acute rejection (AR) episodes and presence of chronic allograft nephropathy (CAN) were collected. Data about office or ambulatory blood pressure measurements were collected for each patient.

Results: 33 patients were transplanted (23 from living related donor and 10 from cadavers) between years 2002 and 2011. The age range of patients for the population under study was 4.3-17.6 years, mean and median values were 13.4 and 14.1 years, respectively. Mean duration of follow-up after renal transplantation was 29.6 months (1–99 months). The prevalence of posttransplant arterial hypertension in our population was 51,5% (17 out of 33 patients). There was no significant difference among hypertensive and normotensive groups with regards to age, cause of renal failure, preemptive transplants, donor type, serum creatinine level at first month after renal transplantation and immunosupressive medications. Among patients in the hypertensive group, 11,7% (n = 2) of the cases experienced at least an episode of AR, compared to 12,5% (n = 2) in normotensive group. The prevalence of CAN in hypertensive group was %23,5 (n = 4). None of the patients in the normotensive group experienced CAN.

Conclusion: Posttransplant hypertension is an important problem in renal allograft recipients.

PS1-THU-423

Single center experience in pediatric kidney transplantation—early complications

I. Ivanisevic*¹, M. Kostic¹, B. Spasojevic¹, A. Peco-Antic², Z. Krstic³, D. Vukanic³, V. Stankovic⁴, M. Petkovic⁴

¹Center of hemodialysis and kidney transplantation, University Children’s Hospital, Belgrade, Serbia, ²Department od nephrology, University Children’s Hospital, Belgrade, Serbia, ³Department of urology, University Children’s Hospital, Belgrade, Serbia, ⁴Department of anesthesiology, University Children’s Hospital, Belgrade, Serbia

Objectives and study: Kidney transplantation is the treatment of choice for end stage renal failure in children. Aim of this study was to analyze early complications after transplantation.

Methods: Retrospective cohort study included 47 patients (49 transplantations) from 6.06.2001. to 1.03.2011. at the University Children’s Hospital in Belgrade. Early complications included complications within 30 days after transplantation.

Results: The mean age of children was 12 ± 4.4 years. Congenital and developmental anomalies of the kidney and urinary tract were the most common cause of renal failure. Renal transplantation was performed after hemodialysis in 83% patients. Thirty eight (77.5%) and 11(22.5%) children received kidneys from living and cadaveric donors, respectively. Living donors transplant recipients were significantly younger than those who received cadaveric graft (p < 0.01) and they had shorter waiting time for transplantation (1.7 vs. 4.8 years). Although cadaveric recipients were older, there was no significant statistical difference in their height compared with patients who received kidney from living donor (p = 0.551). Patient survival during this period was 100%. The most significant complication was the loss of 3 (6.1%) grafts after living related transplantation due to primary afunction. Acute tubular necrosis was observed in 12 (25%) patients and 60% of these patients required dialysis. The most frequent surgical complications were lymphocele collection in 7 (14.3%) patients. There were 7 acute rejection crises (14.3%). Return of the underlying disease happened in 2 grafts (1 patient) (4%). Recovery time was longer and final glomerular flow rate (GFR) was significant lower in patients with cadaver grafts (108.3 ± 33.2 days, 27 ± 9.8 ml/min/1.73 m² vs. 8.7 ± 7.7 days, 68 ± 30.7 ml/min/1.73 m²).

Conclusion: Early complications after kidney transplantation are less frequent in our center then in the reports from other centers.

Key words: kidney transplantation in children, early complications.

PS1-THU-424

Positioning and sedation for native kidney biopsy in children

S. Saleh*¹, M. Newbould², M. Lewis¹

¹Paediatric Nephrology Department, Royal Manchester Children’s Hospital, Manchester, UK, ²Paediatric Histopathology Department, Royal Manchester Children’s Hospital, Manchester, UK

Objective: to assess the success rate of the complications associated with native renal biopsy under general anaesthesia whilst in the lateral position.

Method: 131 native kidney biopsies performed between January 2005 and December 2010 using general anaesthesia and the lateral position were reviewed. Complications were assessed from the medical records. The biopsies were assessed for adequacy by one consultant histopathologist. All children had a full blood count 6 hours post biopsy.

Technique: Under general anaesthesia the patient was placed in lateral position. Both kidneys were identified with ultrasound and the lower pole of the lower kidney was marked,(right lower pole in right lateral position and left lower pole in left lateral position),the distance between skin and cortical surface was measured and the biopsy performed using the automated 16 gauge sprung needle.

Results: Of the 131 patients,69 were male and 62 female. The mean patient age was 10.6 years(range 1 month–18 years). 90% of the biopsies were from the left kidney. 2 cores were achieved with 2 passes in(71.7%). Adequacy specimens for diagnosis were obtained in 129(98.4%). Macroscopic haematuria occurred in 7 patients(5.3%)and resolved completely within 24 hours. No patient needed a blood transfusion. No other complications were reported with 97 patients(74%)being discharged home after 6 hours,11 patients(8.4%)after 24 hours,the remainder being treated as an in patients for an acute renal problem.

Conclusion: This technique for a percutaneous native kidney biopsy in children is quick,safe and effective. There is a low incidence of biopsy related complications,whilst inadequate sampling is rare. The use of general anaesthesia is safer than sedation and the lateral posision is safer than being prone.

PS1-THU-428

Extracorporeal blood purification techniques (EBP) in a treatment of children and adolescents poisonings

T. Jarmoliński*¹, B. Jachimiak¹, D. Runowsk¹

¹Department of Pediatrics, Nephrology and Toxicology, District Children’s Hospital, Szczecin, Poland

Objectives: The aim of the study was to establish importance of EBP in treatment of poisonings in children and adolescents.

Methods: Between 2000 and 2010 28 patients (18 female and 10 male, aged 2–17 year) were treated with EBP, among them 20 pts after suicide attempts. Life threatening toxic substance blood level and/or clinical manifestations of severe intoxication were indications for beginning the treatment.

Results: 22 pts were poisoned with drugs (10 of them used more than one drug), 3 with amanita phalloides (AP), 1 with ethanol and morphine (E + Mf), 1 with methanol (M) and 1 with formaldehyde (F). Treatment delaying time lasted for 4–48 hours, it was unknown in 10 cases. Among drug abusers, 7 pts were poisoned with carbamazepine (drug blood level 33–50 mg/l, toxic level [TL] >15), 5 with paracetamol (16–346 mg/l; TL 4 hours after ingestion >150), 5 with theophylline (37–85 mg/l; TL >20) and 3 pts with acetylsalicylic acid (ASA) (66–149 mg/dl; TL >30). 19 drug poisoned pts were treated with hemoperfusion (HP) on charcoal column (Adsorba, Gambro), 6 pts poisoned with ASA, E + Mf, M, F, iron formula and enalapril had hemodialysis (HD) and in 2 pts who ingested AP, plazmapheresis was performed using device for continuous techniques (Prisma, Gambro). 1 pt with renal and liver insufficiency caused by AP was treated with HP and HD. Double-lumen femoral (26) or subclavian (2) catheters were used as central venous access. In two pts, poisoned with AP and iron, liver failure appeared. Six-year-old boy died after transplantation. Four-year-old girl had successful living related donor liver transplantation 9 years ago. Transient complications of poisoning and/or EBP were observed in 19 pts.

Conclusions: EBP is effective and safe treatment of severe poisonings in children and adolescents. Pediatric toxicological centers should have unrestricted access to such methods of therapy.

PS1-THU-430

Continuous ambulatory peritoneal dialysis (CAPD)—a forgotten modality in children?

D. Athavale*¹, T. Smith¹, M. Lewis¹

¹Department of Paediatric Nephrology, Royal Manchester Children’s Hospital, Manchester, UK

Objectives and study: Despite being the first effective chronic peritoneal dialysis (PD) treatment for children, CAPD is only used in 10% of UK paediatric patients. We, therefore, tried to ascertain whether CAPD remains an effective treatment.

Methods: A retrospective study was undertaken reviewing all paediatric patients commencing PD, both automated (APD) and CAPD for established renal failure (ERF) from September 2002 to August 2010. Demographic data, duration and reason for cessation along with complications were studied. Comparisons of dialysis adequacy between modalities were made.

Results: 69 treatment episodes of PD were studied in 62 patients. 29 patients received CAPD and 33 APD. 6 patients changed from CAPD to APD. One had 2 APD episodes. 40 patients were male and 22 female. CAPD patients were older than APD patients with a median age of 12.8 years (range 5.1–16.6 years) compared to 5.9 years (range 0–19 years) for APD patients (p = 0.004). Median duration of treatment was 16.1 months for CAPD and 18.8 months for APD (p = ns). Peritonitis was slightly more common in CAPD patients at a rate of 1 in 12.2 patient months for CAPD and 1 in 16.4 patient months for APD. 17 patients from each group had peritonitis (p = ns). Full dialysis adequacy was available in 48 treatment episodes (26 APD, 22 CAPD). There was no difference in total kT/V between the groups whilst creatinine clearance (CrCl) was better in the CAPD group (p = 0.024). Looking just at dialysis adequacy both CrCl and kT/V were slightly higher in the APD group but these differences were not significant.

Conclusion: CAPD is an effective treatment for ERF in children. Good clearance can be attained as can acceptable peritonitis rates. It is cheaper than APD and ought to be considered—particularly where resources are limited.

PS1-THU-432

Bioimpedance resistance could be useful method in dry weight assessment in children on hemodialysis

B. Spasojevic*¹, M. Kostic¹, A. Peco-Antic², M. Cvetkovic¹, I. Gojkovic¹, M. Petrovic¹, I. Simic¹, I. Ivanisevic¹, S. Puric¹

¹Center of hemodialysis and kidney transplantation, University Children’s Hospital, Belgrade, Serbia, ²Department of nephrology, University Children’s Hospital, Belgrade, Serbia

Objectives and study: Inferior vena cava diameter (IVCD) presents standard for total volume load assessment in patients on hemodialysis. Bioimpedance resistance (BIR) is still controversial. Aim of this pilot study was to define means of expression for the analyzed parameters (BIR, IVCD) and their value in assessment of dry weight in children on hemodialysis.

Methods: Sixty-two measurements were performed in ten hemodialysis patients (mean age 13.8 ± 4.6 years), 31 before and 31 after hemodialysis. Body mass index (BMI), body surface area (BSA), body weight (BW), systolic and diastolic blood pressure, bioimpedance (resistance-R), IVCD inspiration (IVCDi), IVCD expiration (IVCDe) and IVCD mean (IVCDm) and collapsibility index (CI) were measured before and after dialysis. All patients were divided in three groups based on IVCDm/BSA: hypovolemic (group I), normovolemic (group II, IVCDm 8–11.5 mm/m2) and hypervolemic (group III). Absolute values of R, BW and IVCD were analsyed, as well as their relative values calculated as: ΔR/Rafter, ΔBW/Bwafter, ΔIVCD/IVCD after.

Results: Resistance was in negative correlation with BW, BMI, systolic blood pressure and with all IVCDs. Statistically significant difference was found between R values before and after hemodialysis (p = 0.000). The same was found for BW (p = 0.000) and IVCDm (p = 0.000). Statistically significant difference was found between absolute R value and IVCDm/BSA before (p = 0.015), but it wasn’t found between absolute R value and IVCDm/BSA after hemodialysis (p = 0.075). Statisticaly significant correlation was found between relative values of R and relative values of BW and IVCDm/BSA (p = 0.001, p = 0.042). There was also statisticalaly significant difference in mean R values between groups I and II and between groups I and III (p = 0.044, p = 0.002).

Conclusion: Based on preliminary results relative value of R is more reliable parameter for dry weight assesment then its absolute value, while absolute R values correlate with IVCD in volume overload. Key words: bioimpedance, vena cava, hemodialysis, children.

PS1-THU-434

Does dietary energy intake change after a renal transplant?

S. Flajšman-Raspor* ¹, M. Šubat-Dežulović¹

¹Children’s Renal and Urology Unit, Nottingham Children’s Hospital, Nottingham University Hospitals NHS Trust, Nottingham, UK

Objectives and study: Growth is frequently improved following a paediatric renal transplant however the influence of changes in nutrition is unclear.

The primary aim of our study was to determine whether dietary intake changes before and after paediatric renal transplantation. The secondary aim was to compare growth and energy intake in patients treated with and without steroids as maintenance immunosuppression.

Methods: We routinely record dietary intake using food diaries and calculate energy intake as a percentage of requirement(EAR). We reviewed this information in two groups of patients. Both groups received tacrolimus and mycophenolate mofetil as maintenance immunosuppression. In addition, Group A received regular prednisolone and Group B five days prednisolone following basiliximab induction (TWIST protocol). Data were collected before and at 6 and 12 months after transplant.

Results: 14 patients (10 male(71%), mean age 13.7 years; range 10 to 17 years) were reviewed. The median EAR was 80% before, 89% at 6 months and 90% at 12 months after transplant. This increase was seen in both groups (Group A—89% before to 92% at 12 months, Group B—76% before to 85% at 12 months). Increased growth was seen from before transplant to 12 months after transplant (median weight z-score −1.74 to −0.7, median height z-score −1.92 to −1.27 and median BMI z-score −0.79 to 0.395). Group A trended towards a greater increase in weight than height and had higher BMI z-scores at 12 months (Group A 0.5, Group B 0.135).

Conclusion: Dietary energy intake is increased following a renal transplant and may contribute to increased growth. There is a trend towards increased BMI following renal transplant which may be more marked in patients treated with steroids as part of their maintenance immunosuppressive therapy.

PS1-THU-438

Rotavirus infection in pediatric renal transplant recipient

L. Real Mendes*¹, P. Mendes¹, A. Zagalo¹, C. Simão¹, M. Almeida¹

¹Pediatric Nephrology Unit, Hospital de Santa Maria, Lisbon, Portugal

Introduction: In immunocompromised patients there are multiple causes of diarrhea including infections, drugs, inflammatory or lymphoproliferative diseases.

Case report: A fifteen year-old boy, that had received a renal graft six months earlier (for nephropatic cystinosis), was admitted with severe diarrhea, dehydration, graft dysfunction (Cr:5,6 mg/dl) and cytopenia (leukopenia with neutropenia and anemia). There was a familiar history of a sister with gastroenteritis. In the initial etiologic investigation Rotavirus was detected. No enteric bacterial or parasitic agents were isolated from stool culture. Clostridium difficile, Criptosporidium, Salmonella, E. coli, Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Poliomavirus, Echovirus and Coxsackievirus infection were excluded. Due to the severity and persistence of diarrhea and maintenance of cytopenia 5 weeks after the onset of symptoms, an upper and lower gastrointestinal endoscopy was performed and revealed acute nonspecific infectious colitis. The biopsy was negative for CMV, Adenovírus, EBV, Rotavirus, Herpesvirus, Echovirus and Coxsackievirus. Renal transplant biopsy excluded rejection and bone biopsy was normal.

During hospitalization he was treated with intravenous hydration and anti-diarrheal diet, but due to persistence of abundant watery diarrhea he started therapy with octreotide. He showed progressive improvement of clinical symptoms and he was discharged after 9 weeks of hospitalization and 2 weeks of octreotide. Currently he is clinically stable with normal renal function, maintaining anemia and leukopenia.

Conclusion: Rotavirus can be a cause of severe diarrhea in renal transplant recipients. We suggest screening for rotavirus in these immunocompromised patients, that are very susceptible to hypovolemia.

PS1-THU-439

Early rifle criteria and sepsis in critically ill children

M. Andrade*¹, C. Mangia¹, J. Carvalhaes¹

¹UNIFESP-EPM, Andar, Brasil

Objective: We conducted a study to evaluate the incidence, risk factors and outcome associated with acute kidney injury (AKI) in the first 24 hours after pediatric intensive care (PICU) admission.

Methods: Retrospective study based on the institutional database analyzing 1050 patients admitted from October, 1999 to January, 2005.

Results: Of 1050 patients were admitted, we excluded 78 patients with end stage kidney disease (ESKD). 190 patients (18%) had sepsis diagnosis and 21% had AKI diagnosis. Septic patients were stratified for AKI RIFLE criteria (risk of renal failure, injury to the kidney, failure and loss of kidney function, and end-stage kidney disease). 10% of patients were to the risk category, 8.9% to the injury and 2.6% to the failure. Septic AKI patients for risk, injury and failure had high length of stay (LOS) before PICU (P = 0.00), high PICU and hospital LOS (p = 0.00), lower PaO2 (P = 0.005), pH < 7.2 (P = 0.01), lower hematocrit (P = 0.00), high arterial blood pressure levels (P = 0.00), high urea levels (P = 0.00), lower base excess (P = 0.00), high glucose levels (P = 0.01), worse pulmonary function measures by arterial oxygen tension/fraction of inspired oxygen ratio (P = 0.00) and use of vasoactive drug (P = 0.00), compared with nonseptic. Septic AKI was also associated with high PIM1 and 2 scores and was associated high hospital mortality (34% versus 24%; odds ratio 1.58, 95% confidence interval 0.8 to 3.11).

Conclusion: Septic AKI was frequent in the first 24 hs after PICU admission. It was associated with high biochemical abnormalities and mortality.

PS1-THU-443

Comparison of posttransplantation renal functions in isolated kidney and combined liver-kidney transplantation in children

D. Alaygut*¹, M. Torun Bayram¹, S. Kavukçu¹, A. Soylu¹, M. Türkmen¹, H. Gülay¹

¹Dokuz Eylul University Medical Faculty, Department of Pediatrics, Istanbul Turkey

Introduction: We aimed to compare clinical and laboratory parameters of isolated kidney and combined liver-kidney transplantation recipients.

Patients and methods: Patients who received ≥3 HLA match isolated kidney (Group 1) or combined liver-kidney (Group 2) transplantation during 1993–2010 were evaluated retrospectively for the following parameters: gender, age at transplantation, pretransplant dialysis duration, posttransplant follow-up period, acute and chronic allograft dysfunction, serum biochemical tests (creatinine, BUN, uric acid, calcium, phosphorus, ALP), creatinine clearance, and renal tubular functions (proteinuria, calciuria, FENa, tubular phosphorus reeabsroption -TPR).

Results: There were 28 patients (14 male) in Group 1 and 5 patients (4 male) in Group 2. Mean ages at transplantation and mean pretransplant dialysis period were not different (143 ± 55 vs 115 ± 63 months and 25 ± 28 vs 13 ± 14 months in Group1 vs Group 2, respectively). Follow-up period was 69 ± 41 and 44 ± 39 months in Groups 1 and 2, respectively. There were 8 acute allograft dysfunction (5 acute rejection, 2 infection, 1 drug toxicity) and 8 chronic allograft nephropathy in Group 1, while Group 2 had only 1 chronic allograft nephropathy. However, two groups were not different statistically. When laboratory tests were compared, two groups were only different for calciuria (higher in Group 1) and TPR (lower in Group 1, p = 0.041).

Conclusion: Patients who received ≥3 HLA match isolated kidney or combined liver-kidney transplantation were similar regarding the clinical course and the laboratory tests except for small differences in calciuria and TPR.

PS1-THU-449

Prognostic factors of progressive course of primary glomerulopathies in children

A. Krylova-Alefirenko*¹, A. Sukalo¹, E. Cherstviy¹, T. Letkovskaya¹, N. Tur²

¹Belarus State Medical University, Minsk, Republic of Belarus, ²2nd Minsk Childrens Hospital, Minsk, Republic of Belarus

Predicting of glomerulopathies progression is a difficult problem for nephrologists. We conducted the study to reveal criteria of probable progression of primary glomerulopathies. 35 children with morphologically confirmed primary glomerulopathy were followed after kidney biopsy for at least 12 months (12–72 months, median 22). According to clinical data (proteinuria, blood pressure, GFR, serum creatinine) patients were referred as progressors (n = 10) and non-progressors (n = 25).

Clinical and morphological data were analyzed. Macrophages (CD68+) and myofybroblasts (αSMA+) in kidney biopsy samples were identified immunohistochemically. ROC analysis was used to assess value of each parameter to predict disease progression. Proteinuria was higher in progressors (p < 0,001). AUC (ROC analysis) was 0,864 (p = 0,001) for disease progression. Cutoff point was 647 mg/day, sensitivity 0,8, specificity 0,88. Among morphological features mesangial proliferation, glomerular sclerosis, interstitial fibrosis, tubular atrophy were of high prognostic value for glomerulopathies progression. Glomerular and interstitial macrophages score was significantly higher in progressors (p = 0,003 and 0,020, accordingly).

Mean macrophages number per glomerulus (AUC 0,821, p = 0,004, cutoff point 308, sensitivity 0,8, specificity 0,792) and per mm2 of interstitium (AUC 0,771, p = 0,014, cutoff point 1,2, sensitivity 0,6, specificity 0,833) were found to be informative criteria for progression prognosis. In progressors we revealed elevated number of interstitial myofybroblasts (p = 0,003). In ROC analysis AUC was 0,846, p = 0,002. Cutoff point was 946 myofybroblasts per mm2 of interstitium, sensitivity 0,7, specificity 0,792.

Proteinuria over 647 mg/day, mesangial proliferation over 2 points, presence of glomerulosclerosis, interstitial fibrosis, tubular atrophy, mean macrophages number 1,2 per glomerulus and 308 per mm2 of interstitium, interstitial myofybroblasts over 946 per mm2 are proved to be predictors of probable progression of childhood primary glomerulopathies.

PS1-THU-454

First results of National Pediatric Transplant Programme in Belarus

S.V. Baiko*¹, A.V. Sukalo¹, O.V. Kalachik², V.I. Dubrov¹

¹National Center for Pediatric Nephrology and Renal Replacement Therapy, Minsk, Republic of Belarus, ²National Center for Organs and Tissues, Minsk, Republic of Belarus

Objectives: Patient and transplant survival and influencing factors were reviewed in the 39 children who received a renal transplant in our center in two periods of time 1997–2008 and 2009–Apr. 2011. 2 required the second transplant. Before 2009 only 17 patients were grafted and 47% operations were performed in abroad (Russia-7, Belgium-1).

Methods: Retrospective case series.

Results: Median age at transplantation was 14,1 (7 to 17,66) years in 1997–2008 (1st p-d) and 13,4 (6,75 to 17,75) in 2009–2011 (2d p-d). The graft was carried out from a living related donor in 5,9% (1st p-d) and 20,8% (2d p-d) of the cases (p < 0,05). The immunosuppression was the same in all patients in the 2d p-d: daclizumab (D0 and D14), Tac + MMF + Pred. The underlying diseases were congenital in 17 (70,8%): obstructive uropathies in 4, neurogenic bladder in 4, dysplastic kidneys and nephrophthisis in 3, others in 3 and 7 had acquired diseases in 2009–2011. Overall patient survival at 1 year was 77,8% in 1st p-d and 100% in 2d p-d (p < 0,05). Transplant survival at 1 year was 55,6% in 1997–2008 and 88,9% in 2009–2011 (p < 0,05).

Conclusions: Changing from informed to presumed consent and supporting by government, mass media and ISN have allowed us to improve the situation with pediatric kidney transplantation considerably achieved 24 operations for last 2 years.

PS1-THU-455

Acute kidney injury as a complication of fungal urinary tract infection

K. Kilis-Pstrusinska*¹, A. Jakubowska¹, M. Bagłaj², D. Zwolinska¹

¹Department of Paediatric Nephrology, Wroclaw Medical University, Wroclaw, Poland, ²Department of Paediatric Surgery and Urology, Wroclaw Medical University Wroclaw, Polan

Fungal infections of the urinary tract are relatively rarely recognised in children. We reported two children, who in the course of fungal urinary tract infection (UTI) developed acute kidney injury (AKI). Patient 1: 5-month-old boy, born at fullterm with a birth weight of 2540 g, a high imperforate anus, post colostomy performed on day 2 of life; in the neonatal period hypoplastic right kidney was recognised. Patient 2: a 3-month-old boy, born at 33 weeks gestation, with a birth weight of 2050 g, congenital abnormalities (dysmorphic features, upper and lower limb deformities) and bacterial UTI; micturating cystourethrography demonstrated bilateral grade IV vesico-ureteral reflux (VUR). In our patients the few risk factors of fungal UTI were noted. There were: urinary tract malformations, in one of the boys associated gastrointestinal tract anomalies, longterm antibiotic therapy and also in one of the children prematurity.

In our hospital, the boys were treated due to a bacterial UTI. Despite the use of antibiotic according to sensitivities and antifungal prophylaxis, the children\’s condition suddenly deteriorated. We stated AKI and urine stasis in pyelocalyceal system. Urine culture revealed heavy growth of Candida albicans. Usg showed numerous inhomogenous hyper- and hypoechogenic structures in urinary tract probably being fungal masses. Timely detection and quick institution of intravenous antifungal therapy enabled curing our patients without surgical intervention. In the children the fungal UTI and AKI were caused by coexistence of few risk factors and additional unknown anomalies. In the first boy further investigations demonstrated an additional malformation of the urinary tract (a leftsided ureterocoele and a leftsided grade IV VUR) and an intestino-vesical fistula.

This study shows that fungal UTI in infants can even lead to AKI. In every case detailed analysis of predisposing factors and possibly extended diagnostics is indicated.

PS1-THU-465

Risk of severe bacterial infections after anti CD20 treatment in paediatric patients with idiopathic nephrotic syndrome and kidney transplant recipients

D. Meneghesso¹, G. Ghirardo¹, E. Benetti¹, E. Vidal¹, L. Murer*¹

¹Pediatric Nephrology, Dialysis and Transplant Unit—Department of Pediatrics- Az Ospedal and University of Padova, Padova, Italy

Rituximab (RTX) is a monoclonal antibody that selectively blocks B-cells proliferation, decreasing antibodies production. It has been used for many years in B-cells lymphoma and rheumatoid arthritis. Meta-analyses showed an increased incidence of serious bacterial infections limited to patients with cancer. In kidney transplantation, RTX is used in the treatment of EBV-related-PTLD, acute humoral rejection and de novo/recurrent glomerulonephritides. In adult transplanted patients its use seemed to be associated with a higher risk of serious bacterial infections only in subjects who had previously received ATG. Recently, RTX has been suggested for the treatment of idiopathic nephrotic syndrome (INS), but no data are yet available on infective risk in this population. We analysed the incidence of bacterial infection in a 6 months period after RTX treatment in 25 paediatric patients: 10 kidney transplant recipients and 15 with INS. Paediatric transplant recipients group: 10 patients, mean age 7,8 ± 5,5 years; M/F: 9/10. Clinical indications for RTX therapy were chronic EBV infection in 3, PTLD in 2, humoral rejection in 1, recurrent renal disease in 3 and de novo glomerulonephritis in 1 patient. The median time between kidney transplant and RTX infusion was 8 months (range 0,4–60); the mean number of infused doses (375 mg/m2/dose) was 2.4; six months after RTX infusion, the immunosuppressive maintenance regimen was based on steroids + CsA/FK506 ± MMF. We observed 8 bacterial infections in 7 patients: 4 bacterial pneumonias, 1 Pneumocystis Carinii pneumonia, 1 sepsis after E. Coli pyelonephritis, 1 peritonsillar abscess, 1 St. Aureus bacteriaemia. These infections were observed at an average of 60 days after RTX infusion (range 30–180).

INS group: 15 patients, mean age 11 ± 4 years; M/F: 11/4; 11/15 patients had steroid-dependent NS and 5 steroid-resistant NS. Average time between INS onset and RTX infusion was 69 months (range 8–204); mean number of infused doses was 1,5. Immunosuppressive regimen was based on steroids + CsA/FK506/MMF; immunosoppressive therapy was progressively reduced after RTX infusion and withdrawn after 6 months in 3 patients. Two patients developed localized bacterial infections (paronychia, dental abscess), both 30 days after RTX treatment. All 25 patients (both transplanted and INS) showed 0% B-cells CD20+ and normal IgG levels at the moment of infection. Our results confirm the high incidence of serious bacterial infections after RTX therapy even in pediatric kidney transplant recipients. In INS group, the observed infections were less frequent and serious, despite a longer immunosuppressive treatment before RTX infusion (>5 years) and the fact that 73% of patients still on a double therapy regimen 6 months after RTX treatment. On this basis, we suppose that the level rather than the duration of immunosuppression, or other immunological or non-immunological factors, expose patients treated with RTX to a higher risk of bacterial infections.

PS1-THU-466

Chronic allograft nephropathy and peritubular capillary C4d deposition in protocol renal allograft biopsies

G. Ghirardo*¹, M. Della Vella², E. Benetti¹, E. Vidal¹, S. Centi², L. Murer^1,2

¹Pediatric Nephrology, Dialysis and Transplant Unit—Department of Pediatrics- Az Ospedal and University of Padova, Padova, Italy, ²Laboratory of Kidney Immunopathology and Molecular Biology, Department of Paediatrics, University of Padua, Padova, Italy

The complement factor C4 participates in the classic pathway of complement activation. C4d, a degradation product of complement factor C4, binds covalently to tissues at the site of activation, becoming a permanent marker of antibody-mediated injury. Recently, the role of humoral damage has been underlined not only in acute kidney rejection, but also in chronic allograft rejection. The 7th Banff conference introduced PTC C4d staining as a new marker of humoral rejection and later studies conducted on biopsies made for clinical indications showed an association between PTC C4d staining and a faster decline of kidney function one year after biopsy.

The aim of our analysis was to analyze retrospectively the prevalence of PTC C4d staining on protocol biopsies performed 12 and 24 months after transplantation and with histological features of Chronic Allograft Nephropaty (CAN). Among 365 available biopsies, 54 biopsies with histological features of CAN, performed on 45 paediatric transplant recipients with a mean follow-up of 3.4 years (range 1–5), were evaluated. The mean age of patients (M/F 30/15) was 13,62 ± 6,3 years, range 1,8–26,2. 27 patients received an induction immunosuppression based on anti-CD25 Mab, while 18 received only corticosteroid pulses. Manteinance immunosuppression was based on CsA/FK506 + MMF/AZA + steroids. 10/30 biopsies (33,3%) and 10/24 biopsies (41,6%) performed respectively at 12 and 24 months after transplantation showed a rate of PTC C4d staining higher than 10%; in 6/10 of these biopsies, the observed positivity rate was higher than 30%, both at 12 (66.6%) and 24 (66.6%) months after transplantation. PTC C4d staining was not correlated to the induction therapy received (corticosteroid pulses vs anti-CD25 Mab) or to the maintenance immunosuppressive therapy at 12 and 24 months after-transplantation (CsA vs FK506 and MMF vs AZA). Creatinine Clearance (calculated according to Schwartz’s formula) at 12 and 24 months after-transplantation was compared among three groups of patients: PTC C4d staining <10%, 10–30% and >30%. We found no differences between the groups. Furthermore, we observed no differences comparing the CrCl at 3 and 5 years after transplantation between patients who showed PTC C4d staining >30% at post-transplant 12 and 24 months-biopsies and the other patients.

In our analysis on 54 protocol biopsies with histological features of CAN performed 12 and 24 months after transplantation, we found a high incidence of PTC C4d staining; indeed, about 30% of patients showed a C4d staining in more than 30% of PTC. However, this find does not seem to be associated with a worse outcome of graft function early after transplantation. The role of PTC C4d staining as a predictive marker of kidney function late after transplantation remains to be understood.

PS1-THU-479

Inferior vena cava diameter: a useful method for estimation of fluid status in children on haemodialysis

M. El- Balshy* ¹, A. H. Abd El- Monem¹

¹Benha faculty of medicine, Berket El Sabaa- Menofia, Egypt

Background: Fluid balance is integral component of haemdialysis(HD) treatments to prevent under- or overhydration, both of which have been demonstrated to have significant effects on intradialytic morbidity and long-term cardiovascular complications. The clinical markers alone do not suffice to assess dry weight secondary to changes in lean body mass and body fat, particularly in children. We evaluated the usefulness of inferior vena cava dimeter(IVCD) by ultrasonography as a useful, simple, non-inasive and reliable method for estimation of fluid status in children on HD.

Methods: Fourty four patients on regular HD (mean age 9.8 years) were evaluated clinically including weight, height, blood pressure, periorbital oedema, before, during and after dialysis session. Dry weight was assessed based on the above parameters. Ultrasonographic studies immediately prior, during (half the session) and 10 min following dialysis were performed. IVCD was measured in the supine position, at quiet end expiration, utilizing the subxiphoidal long axis view by the leading edge method. Twenty healthy children were studied as a control group.

Results: Mean IVCD decreased from 7.425 + 1.33 mm to 6.925 + 1.17 mm to 6.293 + 1.18 mm before, during and after HD respectively (p < 0.001). Changes in IVCD were highly significantly correlted with alterations in body weight following HD (p = .000). There was a highly significant statistical increase in IVCD before HD compared to IVCD of the control group (p < 0.001), while there was no statistically significant difference between IVCD after HD in patients group in comparison to control group (p > 0.05). IVCD clearly reflected alterations in fluid status.

Conclusions: Our findings concluded that the usefulness of IVCD measurement as a reliable, non-invasive tool for estimation of fluid status in children on HD. However, the combination of clinical parameters of over- or underhydration and IVCD may accomplish more accurate evaluation of hydration in children on HD and improve their quality of life.

KEYWORDS: Haemdialysis, inferior vena cava diameter, ultrasonography, dry weight, fluid status.

PS1-THU-481

Estimation of GFR in pediatric renal transplant recipients: which formula is best?

E. Comak¹, C. S. Dogan¹, A. Uslu Gökceoglu¹, H. Akbas², A. Dinckan³, A. Gürkan³, M. Koyun* ¹, S. Akman¹

¹Akdeniz University Medical Faculty, Department of Pediatrics, Division of Pediatric Nephrology, Antalya, Turkey, ²Akdeniz University Medical Faculty, Department of Biochemistry, Antalya, Turke, ³Akdeniz University Medical Faculty, Department of General Surgery, Antalya, Turkey

Aim: To compare the formulas used to estimate glomerular filtration rate (GFR) in pediatric renal transplant recipients.

Material-method: Pediatric renal allograft recipients who were followed up between August 2006 and August 2010 at our department were included. GFR was estimated retrospectively using 1870 analysis of BUN, serum creatinine (scre) and cystatin C levels from 126 children. New extended Schwartz formula , which includes all scre, cystatin C and BUN levels was determined to be the gold standard. The correlations of scre-based (classic Schwartz and revised Schwartz) and cystatin C-based (Filler, Larsson, Grubb and Schwartz’s cystatin C) formulas with new extended Schwartz formula were calculated. For statistical analysis, correlation and Blant–Altman tests were used.

Results: A total of 126 children, 70 boys, aged 11.8 ± 3.9 years, were included. A strong correlation was found with GFR levels estimated by all formulas (r = 0.78–0.91, p < 0.001), of which maximum correlation was with revised Schwartz formula (r = 0.91, p < 0.001). Using Blant–Altman analysis, it was found that estimated GFR (eGFR) levels of revised Schwartz, Filler, Grubb, classic Schwartz and Larsson formulas were higher than that of new Schwartz formula (−7.2, −7.9, −11.8, −31.2 −31.2, respectively), whereas eGFR of Schwartz’s cystatin C formula was lower than that of new Schwartz formula (+7.9).

Conclusion: Different formulas using to estimate GFR could give higher or lower GFR levels in pediatric renal transplant recipients. For best results, revised Schwartz or new extended Schwartz formulas should be used.

PS1-THU-486

Ventriculoperitoneal shunts in children on peritoneal dialysis (PD): a survey of the International Pediatric PD Network (IPPN)

N. Dolan* ¹, D. Borzych-Duzalka², M. Fischbach³, L. Pape⁴, I. Principi⁵, N. Printza⁶, A. Suarez⁷, F. Schaefer², B. Warady⁸, C. White¹

¹BC Children’s Hospital, Vancouver, Canada, ²University Children’s Hospital, Heidelberg, Germany, ³Children’s Dialysis Center, Strasbourg, France, ⁴Medizinische Hochschule, Hannover, Germany, ⁵Hospital Pediatrico Humberto Notti, Mendoza, Argentina, ⁶Hippokration General Hospital, Thessaloniki, Greece, ⁷Hospital de Ninos, La Plata, Argentina, ⁸Children’s Mercy Hospital, Kansas City, USA

The simultaneous presence of a ventriculoperitoneal shunt (VPS) and a PD catheter (PDC) in children is exceedingly rare. The risk of ascending or descending infections is difficult to assess due to a paucity of published cases, thus limiting evidence-based decisions as to the suitability of PD as an option for children with, or needing, a VPS.

Objective: Inform best-evidence based practice by collating and disseminating the experiences of members of the IPPN with children having concurrent VPS and PDC.

Methods: An online questionnaire was distributed to all 135 centers participating in the IPPN, 67 of whom responded.

Results: 14/67 centres (21%) reported having treated a total of 17 patients with concurrent VPS and PDC. The children were 0–12 (mean 6.8) years old at the time of the second catheter/shunt insertion. 14/17 had the PDC inserted post VPS. VPS and PDC were present together on average 23 (range 1–60) months. One patient developed an isolated VPS infection temporally unrelated with a peritonitis episode. 12/17 developed peritonitis (18 episodes total) during 263 months at risk (peritonitis rate 1/15 months). No ascending VPS infection or meningitis occurred pre/during or immediately following a peritonitis. 2 patients recovered renal function, 5 received renal transplants, 3 converted to haemodialysis, 4 died and 3 patients are currently still on PD.

Conclusions: This is the largest reported series of children with simultaneous VPS and PDC in situ. During a total of 392 months at risk, no patients developed ascending meningitis secondary to an episode of peritonitis. We propose that concurrent use/ placement of a VPS and PDC be considered a safe and acceptable option in the rare child requiring dialysis and a cerebral fluid shunt.

PS1-THU-496

Renal impairment in toxidermia: about two cases

P. Krug* ¹, S. Le Guillou², M. Chalumeau², P. Niaudet¹, R. Salomon¹

¹Pediatric nephrology, Necker hospital, Paris, France, ²Pediatrics, Necker hospital, Paris, France

Introduction: We report on two patients, who developed toxidermia due to antconvulsivant drugs associated with renal impairment.

Cases report: Patient 1, a 5-year-old girl, suffered from DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) induced by oxcarbazepine, introduced for a first partial seizure, associating skin rash, cholestasis and cytolysis hepatic impairment with eosinophilia (maximal 3100/mm3) and a positive HHV6 serology. She improved after removing oxcarbazepine. Two weeks after the onset, acute renal failure was diagnosed (creatininemia 266 μmol/l) with tubular proteinuria. Renal histology displayed acute tubulo-interstitial nephritis, treated with methylprednisolone shots which normalized the renal function. The outcome consisted in persistent and fluctuant eosinophilia, corticotherapy was progressively tapered, and renal function remained normal. In patient 2, a 15-year-old boy, was observed a rash three weeks after the introduction of carbamazepine for behaviour troubles; He was admitted for impetiginisation with fever, and tubular proteinuria without renal failure. Carbamazepine was removed. A proteinuria (2,8 g/l) with hypoalbuminemia (32 g/l) occurred three weeks later. HHV6 PCR was positive in blood. Renal histology was in favor of minimal change disease, and therapeutic abstention was decided.

Conclusion—discussion: In DRESS syndrome, renal failure occurred in up to 30% of cases, attributed to tubulointerstitial nephritis. Our first patient had a typical renal impairment and an excellent outcome with steroids. However, corticosteroid may be responsible for rebound when decreasing and should be prescribed carefully. In DRESS syndrome, viral infection are often observed, especially HHV6 as observed in our two patients. On the other hand, the association of toxidermia and glomerular proteinuria had not been described before, but we could hypothesize that activation of a population of T cells induced by the drug could lead to podocyte injury, maybe through interleukin secretion. A direct effect of HHV6 on T cells population could also explain the glomerular injury.

PS1-THU-497

The influence of arterial hypertension (AH) and antihypertensive medications on residual renal function (RRF) in children on chronic peritoneal dialysis (PD)

P. Skrzypczyk* ¹, M. Roszkowska-Blaim¹, A. Jander², M. Tkaczyk², D. Drozdz³, K. Zachwieja³, J. A. Pietrzyk³, I. Balasz-Chmielewska⁴, A. Zurowska⁴

¹Department of Pediatrics and Nephrology, Medical University of Warsaw, Warsaw, ²Department of Pediatrics and Immunology with Division of Nephrology, Polish Mother’s Memorial Hospital, Lodz, ³Department of Dialysis, Chair of Pediatrics, Polish-American Institute of Pediatrics Collegium Medicum Jagiellonian University, Cracow, ⁴Department of Nephrology and Arterial Hypertension of Children and Adolescents, Medical University of Gdansk, Gdansk

RRF plays important role for patients on PD. Adult studies show inconsistent data on impact of AH and antihypertensive medications (AHM) on RRF.

Objective: To assess influence of AH and AHM on RRF in children on chronic PD.

Methods: Study group consisted of 101 children (44 CAPD, 57 APD) with preserved RRF. In all patients before PD initiation and every 12 months RRF on basis of daily diuresis [ml/kg/24h], [ml/m2/24h] and normalized residual clearance of creatinine (NRCCr), presence of AH and AHM usage were evaluated. Observation period was 36 months.

Results: AH was found in 63 (62.4%) children: CAPD—31 (70.5%), APD—32 (56.1%) (ns). Most commonly used AHM were: calcium channel antagonists (CCA)—41 (65,1%), ACEi—29 (46,0%), furosemide—30 (47.6%). During first 24 months in APD group patients with AH had higher (p < 0.005) rate of decline of daily diuresis [ml/kg/24h], [ml/m2/24h] than normotensive ones. No influence of CCA, ACEi, furosemide and beta-adrenolytics on rate of decline of daily diuresis [ml/kg/24h], [ml/m2/24] and NRCCr in first 12 months in CAPD, APD groups was found. During 36 months of PD 20 (19.8%) children preserved (10 CAPD,10 APD) and 22 (21.8%) lost diuresis (7 CAPD,15 APD). Prevalence of AH in patients with preserved RRF was significantly lower compared to the group with RRF loss: CAPD—5/10(40.0%) vs. 7/7 (100.0%) (p < 0.05), APD—3/10 (30.0%) vs. 13/15(86.7%) (p < 0.01).

Conclusions: 1. AH is a risk factor for anuria in children on chronic peritoneal dialysis, especially treated with APD. 2. The choice of AHM does not influence rate of decline of RRF in children on PD.

PS1-THU-499

Epidemiology of hantavirus infections in pediatric patients compared to adults in Germany in the last 10 years

R. Goldwasser* ¹, B. Tönshoff1, M. Zeier²

¹University Children’s Hospital Heidelberg, Germany, ²Department of Nephrology, University Hospital Heidelberg, Germany

Objectives: Infection with hantaviruses is associated with significant morbidity and mortality worldwide, causing beside others the hemorrhagic fever with renal syndrome. Hantavirus infection is acquired by inhalation of aerosolized virus containing particles from infected rodents. Data on the epidemiology in pediatric patients are scarce and very little is known on the epidemiology of different hantavirus species in the pediatric population in Germany.

Methods: We therefore analyzed data on Hantavirus infections in pediatric and adult patients in Germany reported to the German Institute for Infectious Disease Epidemiology (Robert Koch-Institute in Berlin) from 2001 to mid February 2010.

Results: The reported overall incidence of Hantavirus infections varied significantly between 72 cases in 2006 and 1688 cases in 2007 (Figure). The proportion of pediatric patients ranged from 2.2% in 2009 to 9% in 2003, being significantly lower than expected (20% of the entire population in Germany belongs to the pediatric age group). 76% of pediatric cases occurred in the age group 15–19 yrs, although individual cases in toddlers have been reported. In 2007 there was an outbreak of Hantavirus infection. Furthermore infections with the Puumala virus accounted for the majority of hantavirus infections both in adult (88%, Figure) and pediatric patients (91%). Other detected virus species comprised Dobrova virus (adult 1.4%, pediatric 1.8%), Hantaan virus (adult 0.8%, pediatric 0.9%) and Belgrad virus (adult 0.03%, none pediatric). All these virus species are associated with the HFRS. Andes virus infections, the only hantavirus transmitted by person-to-person contact, as well as species causing the HCPS did not occur.

Conclusion: Hantavirus infections in Germany affect mainly adult patients and adolescents. Outbreaks as observed in 2007 are most likely due to regional increases of mice populations secondarily to the climate change.

PS1-THU-500

Late onset of Parvovirus B19 induced anemia following renal transplantation by children

R. Goldwasser* ¹, B. Tönshoff¹, D. Kiepe¹, H. H. Hirsch², P. Schnitzler³

¹University Children’s Hospital Heidelberg, Germany, ²University Hospital Basel, Department of Clinical and Transplantation Virology, Basel, Switzerland, ³University Hospital Heidelberg, Department of Virology, Heidelberg, Germany

Objectives: Infection with Parvovirus B19 in children after renal transplantation is known to be due to Immunosuppression (to avoid transplant rejection) and lack of protective antibodies. This infection therefore takes place mainly in the early phase after transplantation. It is mostly associated with artropathy, encephalitis, myocarditis and/or anemia.

Methods: We test our kidney-transplanted patients routinely in the beginning on monthly and later on yearly basis for Parvovirus assay in blood (IgG, IgM and PCR) along with other renal functions and examinations.

Results: One of our patient (15 year old) whom underwent kidney transplantation in 2001 got immunosuppression therapy with xxxxxxx. This patient had his yearly routine examination showing always a negative assay result for Parvovirus B19. In January this year (after 9 years) he presented the first time with positive Parvovirus B19-DNA assay (>1011 copies/ml) followed by severe hyporegenatoric anemia (Hb 5,08 g/dl) leading to erythrocytes transfusion.

Conclusion: Parvovirus B19 infections affect mainly otherwise healthy children leading to benign erythema infectiousum. In transplanted patients (adults as well as children) this may cause arthritis, encephalitis, myocarditis and/or anemia. It manifest in the majority of the cases in the first 9 weeks post transplantation. In our case we saw that 9 years after the child underwent a renal transplantation, he suffered from sever hyporegenatoric anemia (sudden onset) due to new diagnosed infection with Parvovirus B19. As his viral assays were always negative we believe this may be due to community-acquired infection as a consequence of immunosupression rather than donor acquired one. As a therapy measure immunosuppression must be reduced and in acute phase IVIG therapy is indicated.

PS1-THU-502

Activation of innate immunity in Henoch-Schoenlein purpura with and without nephritis: increased toll-like receptors expression in circulating lymphomononuclear cells

R. Camilla* ¹, E. Loiacono¹, L. Morando¹, R. Gallo¹, M. Conrieri², M. Bianciotto², F. M. Bosetti², L. Peruzzi¹, A. Amore¹, R. Coppo¹

¹Nephrology, Dialysis and Transplantation—Regina Margherita Hospital—Turin, Italy, ²Pediatric Emergency Unit, Regina Margherita Hospital—Turin, Italy

Objective and study: We recently reported (Clin Exp Immunol 2009, 159:73 81) that Toll-like receptors (TLR4) are up-regulated in circulating mononulcear cells (PBMC) from patients with primary IgA nephropathy (IgAN), in agreement with an involvement of mucosal innate immunity. Henoch-Schoenlein purpura (HSP) is a systemic vasculitis with renal pathology features indistinguishable from primary IgAN. We aimed this study at investigating whether PBMC from patients with HSP present with an upregulated TLR expression, and whether it is correlated with renal involvement.

Methods: The expression of TLR2, TLR4, and TLR9 was detected in PBMC of 28 children with HSP (7.6 +/− 2.2 years old) at onset, 15 without urinary signs and 13 with renal involvement (all with hematuria and 9 also with proteinuria >0.250 mg/day), in 15 children with primary IgAN (10.9 +/− 3.7 years), 27 children with nephrotic syndrome (NS) and 40 healthy controls (HC). TRLs were detected by cell sorter analysis (FACS), expressed in fluorescence intensity (MIF) and mRNAs quantification by real time PCR(Taqman), calculated normalizing values with Abelson gene expression.

Results: Patients with HSP showed, in comparison to healthy controls, significantly increased expression of TLR2 (4.22 +/− 1.51 versus 3.05 +/− 0.66 MIF, p = 0.021), TLR4 (2.28 +/−0.71 versus 1.71 +/− 0.44 MIF, p = 0.025), and TLR9 mRNA (2.91 +/− 2.01 versus 0.73 +/− 0.43, p = 0.005). No difference was found in HSP with or without renal involvement. HSP showed, in comparison with children with primary IgAN, higher levels of TLR9 and TLR4 mRNAs (TLR9: 2.91 +/− 2.01 versus 0.91 +/− 0.64, p = 0.012; TLR4: 2.94 +/−2.35 versus 1.64 +/− 1.27, p = 0.004). No altered expression of TLR2, -4, and −9 and their corresponding mRNAs was detected in patients with nephrotic syndrome with respect to healthy controls.

Conclusions: This is the first report of upregulation of TLRs during HSP with or without renal involvement, suggesting the activation of innate immunity system.

PS1-THU-505

Vitamin D deficiency is associated with short stature and may influence blood pressure control in paediatric renal transplant recipients

R. Shroff* ¹, C. Knott¹, A. Gullett¹, D. Wells¹, S. Marks¹, L. Rees¹

¹Great Ormond Street Hospital for Children NHS Trust and Institute of Child Health, London, United Kingdom

Background: Vitamin D deficiency is common in adult renal transplant recipients, but data in children are scarce. Vitamin D is not simply a ‘calcaemic’ hormone but plays a key role in the prevention of cardiovascular disease and maintenance of bone health, which are common problems in the transplant recipient. We hypothesised that vitamin D deficiency is common in paediatric renal transplant recipients, and may be associated with bone disease, renal function and blood pressure control.

Patients and methods: We recruited 106 children during the winter/spring season who had a functioning renal transplant for at least 3 months. Levels of ‘nutritional’ 25 hydroxyvitamin D [25(OH)D] and the hormonal form 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured and correlated with clinical and biochemical parameters.

Results: 92% of renal transplant patients were 25(OH)D deficient and 9% had severe deficiency. Despite alfacalcidol supplementation in 59 (56%) patients, parathyroid hormone was elevated in 58 (55%) and showed a strong inverse correlation with 25(OH)D (p = 0.0003, r = 0.61) but not with 1,25(OH)2D levels. Height standard deviation score (SDS) showed an inverse correlation with 25(OH)D levels (p = 0.007, r = 0.42) and also time post transplantation (p = 0.02, r = 0.23); both were significant and independent predictors of height SDS. 25(OH)D correlated with systolic BP SDS (p = 0.02, r = −0.26); this association was lost on multiple regression analysis, but 25(OH)D was the only modifiable risk factor for hypertension. There was no correlation with estimated GFR or proteinuria.

Conclusion: 25(OH)D deficiency is common in paediatric renal transplant recipients and correlates with hyperparathyroidism and short stature. Also, 25(OH)D deficiency may be a modifiable risk factor for hypertension in transplant recipients. Further studies are required to test if routine supplementation with ergo or cholecalciferol is safe and effective in children after renal transplantation.

PS1-THU-506

Ergocalciferol supplementation in children with CKD delays the onset of secondary hyperparathyroidism—a randomised, double-blinded placebo controlled study

R. Shroff* ¹, M. Wan², A. Gullett¹, S. Ledermann¹, R. Shute¹, C. Knott¹, D. Wells³, L. Rees¹

¹Renal Unit, Great Ormond Street Hospital for Children NHS Trust and Institute of Child Health London, United Kingdom, ²Clinical Research Facility, Great Ormond Street Hospital for Children NHS Trust and Institute of Child Health London, United Kingdom, ³Department of Chemical Pathology, Great Ormond Street Hospital for Children NHS Trust and Institute of Child Health London, United Kingdom

Background: Vitamin D deficiency is thought to be an important contributor to the development of hyperparathyroidism, and is also independently associated with a risk of cardiovascular and bone disease. We hypothesise that nutritional vitamin D (Ergocalciferol) supplementation in children with early CKD delays the onset of secondary hyperparathyroidism.

Study: design We conducted a prospective, randomised, double-blinded, placebo controlled study in children with CKD stages 2–4 who had 25-hydroxyvitamin D [25(OH)D] deficiency (defined as levels <75 nmol/L). Ergocalciferol (or a matched placebo) were given daily as per K/DOQI guidelines with an intensive replacement phase for 3-months followed by a maintenance phase. The primary end point was the time to development of hyperparathyroidism (defined for this study as parathyroid hormone [PTH] levels above normal on 2 consecutive occasions). 25(OH)D levels were measured by tandem mass spectrometry and monitored 3-monthly.

Results: 73 children with a mean age of 8.4 ± 4.7 years and mean estimated GFR 53 ± 14.8 ml/min/1.73 m² were screened. 47 children were 25(OH)D deficient and randomly assigned to receive Ergocalciferol or placebo. 20 children in each arm completed the study—2 withdrew consent, 3 refused medication, 1 started vitamin D supplements and 1 was lost to follow-up. The 2 groups were well matched for age, race, eGFR and season when recruited. There was no difference in the mean calcium intake from diet and phosphate binders between the groups. 3/20 children on Ergocalciferol and 9/20 on placebo developed hyperparathyroidism. Children on Ergocalciferol had a significantly longer time to development of secondary hyperparathyroidism (p = 0.05; 95% confidence intervals 0.1 to 1.00) as compared to those on placebo. There were no Ergocalciferol related adverse events. 25(OH)D levels >100 nmol/L were required to achieve normal levels of ‘active’ 1,25-dihydroxyvitaminD.

Conclusion: Ergocalciferol is an effective, safe and cheap treatment that delays the development of secondary hyperparathyroidism in children with mild-moderate CKD.

PS1-THU-519

Characteristics of acute postinfectious glomerulonephritis in Montenegrin children

S. Pavićević* ¹, D. Majić¹, G. Marković¹

¹Clinical Center of Montenegro, Institute for Children’s Diseases, Podgorica, Montenegro

Objective: Although rare in developed countries, acute postinfectious glomerulonephritis (APIGN) is still present in our region. The aim of the study is to analyse demographic, clinical and laboratory characteristics of APIGN in children in Montenegro.

Method: In this retrospective study we analysed records of 46 children (aged three to 15 years) hospitalized in our Institute from january 2001 through january 2011 due to APIGN.

Results: 29 out of 46 children were male (63,04%). There were 1/5 (19,56%) from coastal region of Montenegro, the others lived in central and nothern part. Most of these patients were hospitalized during autumn and winter period (78,26%). Skin infection and streptococcal throat infection with typical latent period preceded in 7 (17,39%) and 31 (67,39%) children, respectively. Macroscopic haemathuria was noticed in 34 children (73,91%). The others (12) had microhaemathuria with severe hypertension in 7 of them (58,33%). High blood pressure levels were measured in 28 patients (60,86%). Seven children had symptomatic hypertension. Transitory nephrotic proteinuria was observed in 6 children (13,04%). Antistreptolysin O titer was elevated at first measurement in 30 children (65,21%). C3 and C4 levels were decreased in 40 (86,95%) and 12 (26,08%) children, respectively. Three patients were diagnosed with posterior reversible encephalopathy syndrome.

Conclusion: APIGN is mainly benign disease but due to potentially severe clinical manifestations it has to be carefully evaluated in acute phase.

PS1-THU-520

Acute kidney injury: classification and prognosis

Z. Sen* ¹, N. Cakar², N. Uncu², N. Kara², B. Acar²

¹Deparment of Pediatrics, Ministry of Health Dıskapı Children’s Hospital, Ankara, Turkey, ²Deparment of Pediatric Nephrology, Ministry of Health Dıskapı Children’s Hospital, Ankara, Turkey

Aim: The aim of this study was to investigate the etiological factors, determination of the level and prognosis of the AKI according to RIFLE and evaluation of the AKI with using RIFLE criteria routinely.

Materials and methods: 72 patients either who were hospitalized due to AKI diagnosis or of whom AKI was developed during the clinical hospitalization at The Ministry of Health, Ankara Children Health Diseases Hematology-Oncology Education and Research Hospital between May 2008–July 2010 were analyzed.

Results: The mean age of 72 patients [42 (58.3%) males, 30 (41.7%) females] was 54.18 ± 71.2 months. Dehydration was the most frequent etiological factor with a ratio of 30.6%, which was followed by hypoxy (19.4%), sepsis (16.7%) drug-induced (12.5%) and hemolytic uremic syndrome (9.7%). The ARF can be classified in types of prerenal, renal and postrenal (18.1%, 76.4% and 5.6% respectively). %61.1 of the cases were oliguric , %19.4 of the cases were anuric. According to the RIFLE criteria, 11 (15.3%) patients were in risk, 18 (25%) patients were in injury, 43 (59.7%) patients were in failure category. The mortality rate was %26.4. Male sex, mechanical ventilation (MV), nephrotoxic drugs, hospitalization before the development of AKI, oliguria and delay in nephrology consultation were found to be associated with increased mortality (p < 0.05). Mortality rate was %10.7 in risk, %31.5 in injury and %57.8 in failure categories.

Conclusion: The risk of AKI was higher in the patients who have received MV and extended period of hospitalization. Mortality rate was associated with increasing the level of AKI.

PS1-THU-525

Protocol biopsies in pediatric renal transplant recipients on cyclosporine versus tacrolimus

B. Aoun* ¹, S. Decramer², F. Bandin², C. Azema¹, R. Vitkevic¹, T. Ulinski1³

¹Pediatric Nephrology, Armand Trousseau Hospital, APHP, Paris, France, ²Pediatric Nephrology, CHU Toulouse, France, ³Université Pierre et Marie Curie, Paris 6, France

Protocol biopsies have been useful for the detection of subclinical rejection and early signs of anti-calcineurin toxicity.

We included in our prospective study all transplanted children from two centers over 24 months (2006 to 2008) and studied the results of protocol biopsies three and 12 months post transplant in patients on cyclosporine A (N = 26) and patients on tacrolimus (N = 10).

All patients received basiliximab induction and were on mycophenolate mofetil with a starting dose of 600 mg/m2 twice daily (dose adapted after four point pharmacokinetic investigations) and prednisone (initially 2 mg/kg/d, followed by tapering down to 0.15 mg/kg/d on day 90). Thirty six kidney biopsies were performed during the first three months; 28 were protocol biopsies and eight were performed after an increase of serum creatinine. Twenty six patients were started on CyA and ten on FK. Among the patients on CyA (N = 26), eight rejections were found and none in patients on FK (N = 10). No biopsies for elevated serum creatinine were performed in patients on tacrolimus in the first year post transplant. There were no differences in patient age or HLA incompatibilities.

Conclusion: Protocol biopsies seem to be of interest, in particular for patients on CyA. Patients on tacrolimus had less acute rejection episodes during the first six months post transplant.

PS1-THU-526

Procalcitonin serum levels in hemodialyzed children—a useful marker for bacterial infection?

L. Tostivint¹, B, Aoun* ¹, C. Azema¹, T. Ulinski^1,2

¹Pediatric Nephrology, Armand Trousseau Hospital, APHP, Paris, France, ²Université Pierre et Marie Curie, Paris 6, France

Infectious complications are a major problem in hemodialyzed (HD) children. Differentiation between bacterial and viral infections is often difficult. In order to treat patients rapidly a sensitive and specific biological marker for bacterial infections would be of interest. Procalcitonin (PCT) has been recognized as an early, sensitive and specific marker for bacterial infections in children with normal renal function.

We have retrospectively analyzed PCT serum levels in end-stage renal disease children on hemodialysis who presented with febrile episodes attributed to bacterial or viral infections. Between 2006 and 2009, twenty-three patients (age 12.3 ± 6.2 years) were included and 35 febrile episodes were identified in 16 out of 23 patients.

Mean time of infectious episode after the onset of HD treatment was 3.9 ± 4.2 months. Time interval until the first bacterial infection was 1.9 months (range 8 days to 2 months). PCT levels were significantly higher in the group with bacterial infections than in the group with no identified infectious agent, presumably viral infections (101.5 ; 1.18–976.4 ng/mL vs. 0.98 ; 0.47–510 ng/mL, p < 0.01). However, very high PCT levels between 5.27 and 510 ng/mL were noted in 7 infectious episodes without identified agent and with clinical signs for benign viral upper respiratory tract infection. PCT levels were positively correlated with CRP levels (R = 0.61 ; p < 0.0002). PCT has a small molecular weight and is eliminated partially by glomerular filtration. Reduction of renal PCT clearance in children on HD is probably the reason for increased PCT levels even in presumably viral infections. Less stimulation of PCT synthesis during viral infections seems to be sufficient for a dramatic PCT serum levels increase. Therefore, PCT levels should be interpreted with caution in the ESRD population.

PS1-THU-528

Estimating glomerular filtration rate in children and young adults

V. de Souza* ^1,2, L. Selistre², M. Rabilloud^4,6, B. Kassai^3,4, A. Hadj-Aissa², B. Ranchin¹, P. Cochat^1,2,4,5, L. Dubourg^1,2,4,5

¹Département de Néphrologie Pédiatrique, Hospices Civils de Lyon, Lyon, France, ²Exploration Fonctionnelle Rénale et Métabolique, Hospices Civils de Lyon, Lyon, France, ³EPICIME, Lyon, France, ⁴Université Claude Bernard, Lyon, France, ⁵FRE 3310, CNRS, Lyon, France, ⁶Service de Bioestatistique des Hospices Civils de Lyon, Lyon, France

Objectives and study: Many formulas for estimating GFR have been proposed using plasma creatinine (PCr); however, each equation has been developed for specific populations so that it is harmful to investigate other groups. We aimed at evaluating 5 formulas based on PCr in different age groups of both children and young adults.

Methods: Inulin clearance (iGFR, ml/min/1.73 m²) was measured in 439 children and young adults (1–25 years, 238 males) between 2003 and 2010. Patients were divided into 3 groups: 1- children (<13 years, n = 218), 2- teenagers (13–18 years, n = 142) and 3-young adults (18–25 years, n = 79). Five formulas were applied: Schwartz 2009 (k = 36.5); local Schwartz (Schwartz formula with our laboratory-specific optimized value of k: 37 in boys >13 yr and 33 in others), Cockcroft-Gault, MDRD and CKD-EPI. The agreement between formulas and iGFR was assessed by Bland Altman method and Lin concordance correlation coefficient.

Results: The mean ± SD iGFR in group 1-2-3 were 94 ± 34, 89 ± 34, and 77 ± 30, respectively. The Lin coefficients(IC 95%) for the 5 formulas were: 0.78(0.73–0.83), 0.84(080–0.88), 0.73(0.66–0.78), 0.17(0.14–0.21), 0.25(0.21–0.30) in group1; 0.79(0.73–0.85), 0.82(0.76–0.87), 0.58(0.49–0.65), 0.43(0.36–0.51), 0.51(0.43–0.59) in group 2; and 0.77(0.67–0.84), 0.75(0.65–0.83), 0.7(0.59–0.79), 0.74(0.63–0.82), 0.76(0.66–0.84) in group 3, respectively. In groups 1 and 2, local Schwartz had the best performance with a Bland Altman mean-difference of 2.90(±20.46) and 1.31(±30.17) and Lin of 0.84(0.80–0.88) and 0.82(0.76–0.87), respectively. In group 3, performance of all formulas was similar.

Conclusions: In children and adolescents, formulas established in adult populations (Cockcroft, MDRD and CKD-EPI) cannot be used and the Schwartz 2009 should be recommended. In young adults, the performance of paediatric and adult formulas are similar. However, despite the good performance of these formulas, they all display considerable limits of agreement and GFR measurement is recommended when a precise determination of GFR is needed.

PS1-THU-532

Is plasma SDMA a suitable marker of renal function in children and adolescents?

A. Wasilewska¹, K. Taranta–Janusz*¹, W. Zoch–Zwierz¹, J. Michaluk – Skutnik¹, J. Stypułkowska¹

¹Department of Paediatrics and Nephrology, Medical University of Bialystok, Poland

Objectives: The purpose of this study was to identify the role of plasma symmetric dimethylarginine (pSDMA) as a useful marker of renal function in children.

Patients and methods: The study group consisted of 35 patients with chronic kidney disease (CKD) stages 1–5 (median age 11.5 yrs). Control group included 42 age—matched healthy children. Immunoenzymatic ELISA commercial kits were used to measure plasma SDMA and serum Cystatin C (Cys C) concentrations.

Results: We found plasma SDMA and serum Cys C levels to be significantly elevated in all CKD patients in comparison with healthy controls (p < 0.05). Plasma SDMA level in children was increased at early stages of CKD (stage 1 and 2) (p < 0.01). There was also a significant difference in pSDMA concentration between stage 3 and stages 1 and 2 (p < 0.01). No difference in pSDMA levels was found between stage 3 and stages 4 and 5 of CKD.

Increase in cystatin C concentrations depending on CKD stage was less rapid than that observed in pSDMA levels. ROC analyses have shown that plasma SDMA is a better diagnostic tool than creatinine for identifying renal dysfunction in healthy children (GFR >90 ml/min/1.73 m²) and for detecting patients with early impairment of GFR (>60 ml/min/1.73 m²).

Conclusion: Increased plasma SDMA and serum Cys C levels were found in CKD children. Further studies are required to confirm a potential application of plasma SDMA and cystatin C as a useful biomarkers for the diagnosis and progression of chronic kidney disease.

PS1-THU-704

Reproducibility of the body composition monitor in healthy children

S. Eerens* ¹, J.H. Vander Lee², A. Bael¹, D. Trouet¹, K. Van Hoeck¹

¹University Hospital Antwerp, Edegem, Belgium, ²Academic Medical Center, Amsterdam, The Netherlands

Objectives and study: The Body Composition Monitor is a bio-impedance spectroscopy developed to measure Total Body Water (TBW), Extracellular Water (ECW), Intracellular Water (ICW) and Lean Tissue Mass (LTM)in dialysis patients. FAT mass and overhydration (OH) are calculated from these values.

The aim of this study was to investigate the intra and inter rater reproducibility of the Body Composition Monitor in children.

Methods: Twenty healthy children (11 boys) aged 3 to 17 years, were measured twice by four different raters from a group of eight. Each rater, representing one of 8 pediatric nephrology centers in Belgium and The Netherlands, measured ten children twice. Reproducibility was assessed using the Bland-Altman method and by calculating Intraclass Correlation Coefficients (ICC).

Results: For none of the parameters a systematic difference was found between pairs of measurement by the same rater. The Limits of Agreement were largest for LTM, i.e. -1.3 to 1. The intra and inter rater ICCs were all 0.99 for TBW, ECW and LTM.

Conclusion: The intra and inter rater reproducibility for the Body Composition Monitor in healthy children is very good. We decided to use it in a larger international study with local investigators to asses fluid status in children with renal replacement therapy.

PS1-THU-705

Neurological development in 21 children on peritoneal dialysis during infancy

H. Laakkonen* ¹

¹Hospital For Children And Adolescents, Helsinki University Central Hospital, Helsinki, Finland

The neurological development of infants on peritoneal dialysis (PD) is a rarely studied topic. The infants are the most demanding patient group on PD with inferior growth, more complications, and higher mortality compared to that in older children, and thus they are susceptible to neurological sequelae.

In this prospective study we enrolled 21 patients under two years of age at the onset of PD (mean 0.59 ± 0.33 years). These patients were evaluated regularly by a neurologist, otologist, physiotherapist and occupational therapist at the beginning of PD and during PD. The neuropsychological tests were collected and evaluated in all patients at least five years old. The brain images before PD, during PD and two years after renal transplantation were reviewed. Hearing was tested during PD and a more precise hearing test was carried out after renal transplantation.

Eleven of 21 patients (52%) had a risk factor for their development, either from their prenatal or neonatal period or from a co-morbidity. All infants tolerated PD well. At the end of the study, 71% of the children had some neurological abnormality. In 29% this entailed a major impairment (all with pre-PD risk factors) and in 43%, only a minor impairment. Brain infarcts were detected in four patients (19%) and other ischemic lesions or periventricular leucomalasia were found in three (14%). Three patients (14%) developed a hearing defect that required the use of a hearing aid. The mortality during PD was only 5%.

PD is a safe treatment modality for end-stage renal failure in infants. Almost two thirds of the children treated with PD in infancy had a neurological impairment detected during our study period. Whereas some patients had risk factors for their development, their neurological problems did not progress during PD. Patients without risk factors tolerated PD well without neurological consequences.

PS2-FRI-001

Non-calculus signs and symptoms of hyperoxaluria and hyperuricosuria in children: a single experience

B. Fateme* ¹, P. Younes¹, T. Mojtaba¹, E. Behzad¹, N. Eqlim¹

¹Research Center of Nephrology and Urology,Baqyatallah Medical School University, Teheran, Iran

Background and aims: Non-calculus presentations of hyperoxaluria (HX) and Hyperuricosuria (HU) are not common. The aim of this study was to investigate the relationship of symptomatic non-calculus idiopathic HX, HU and both of them with dysuria, failure to thrive (FTT), recurrent urinary tract infection (UTI), dysmorphic red blood cells (RBCs) and abdominal pain in children.

Methods: A cross sectional study was done on 58 children who were aged less than 14 years with history of persistent microscopic or macroscopic hematuria with HX and/or HU, regardless of having renal calculi, between October 2007 and October 2008. The patients were divided into three groups according to the type of crystalluria (I, 10 HX; II, 20 HU; and III, 28 HX + HU).

Results: The common presenting symptoms were abdominal pain (63%) and dysuria (45%). FTT frequently occurred in female (68%). No significant relation was seen between the groups in terms of gender, macroscopic hematuria and recurrent UTI. We found that dysuria, positive family history, FTT, abdominal pain and dysmorphic RBCs in patients with HX were higher when compared to HU group. Moreover, logistic regression analysis showed the higher odds ratio of FTT, abdominal pain and dysmorphic RBCs in patients with HX + HU group when compared to patients with HU.

Conclusion: Although our study showed that non-calculus symptoms and signs of crystalluria such as dysmorphic RBCs, FTT, abdominal pain and dysuria are frequently seen in children with HX, however, further studies are needed.

PS2-FRI-003

Gitelman syndrome as a cause of psychomotor retardation in a toddler

S. Skalova* ¹, D. Neumann¹, P. Lnenicka², J. Stekrova²

¹Department of Pediatrics, University Hospital Hradec Kralove and Faculty of Medicine in Hradec Králové, Charles University in Prague, Prague, Czech Republic ²Institute of Medical biology and Genetics, 1st Medical Faculty, Charles University in Prague, Prague, Czech Republic

Introduction: Gitelman syndrome (GS)is an autosomal recessive tubulopathy due to loss of function mutation in SLC12A3 gene encoding thiazide-sensitive NaCl co-transporter in the distal convoluted tubule. GS is characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria and low-to-normal blood pressure. Clinical signs are rarely apparent before five years of age.

Case report: 18-month old boy was referred to pediatric tertiary healthcare center because of psychomotor retardation. Psychomotor retardation was apparent after four months of age, at the age of 12 months he was still unable to sit, stand up or to crawl. Basic laboratory evaluation revealed hypokalemia (serum potassium level 2.7 mmol/L), metabolic alkalosis (pH 7.483, base excess +2.2 mmol/L, standard bicarbonate 26.5 mmol/L) and hypocalciuria (urinary calcium/creatinine ration below 0.1 mmol/mmol. The values of serum sodium, calcium and magnesium were within normal reference range. The serum level of aldosterone was high (1.9 nmol/L). Other results regarding the differential diagnosis of psychomotor retardation were normal. A working diagnosis of GS was established, which was further confirmed by genetic analysis, where three different mutations were detected. Two mutations (c.2576T >C and c.2929C >T, respectively) were considered as causal ones, with patient’s parents being the heterozygous carriers. Oral supplementation with potassium chloride was started, resulting in normalisation of serum potassium level.Within one month of supplementation a significant psychomotor improvement was apparent. Currently, the boy is 5 years of age with quite normal level of psychomotor development.

Conclusion: This case report provides a rare manifestation of GS in infancy and early childhoood where hypokalemia resulted in psychomotor retardation. In spite of being a rare disorder, GS has to be considered in children with developmental delay and muscle weakness.

PS2-FRI-005

Incidence number of relapsing episodes after two years used of enteric coated mycophenolate sodium (EC- MPS) in patients with SDNS

G. Vallejo* ¹, M. Liern¹, V. Dereyes¹

¹Children’s Hospital Ricardo Gutiérrez, Buenos Aires, Argentina

Objective: To evaluate the number of relapsing episodes after of used EC-MPS in the treatment of patients with SDNS. To evaluate the steroid’s adverse events after used EC-MPS. Material and METHODS: Number of treated patients: 16 (9 males). Age: Mean 7 years (r: 3.5–9). Mean time to treatment with EC-MPS: 12 months (r:9–12). Mean time to control after of used EC-MPS: 24 months (r: 28 m–40 m). Inclusion criteria: Glomerular filtration rate (GFR) > de 60 ml/min./1.73 m² ,adverse events due to corticosteroids (hypertension, intraocular hypertension, delayed growth, gastric non tolerability (erosive gastritis), cutaneous lesions, and signed informed consent Exclusion criteria: Secondary nephrotic syndrome, leukopenia(below <4000/mm3), tumoral or infective active disease. Treatment: EC-MPS: 450–1080 mg/m2/day, methyl prednisone was progressively decreased by10 mg/m2 each 8 weeks until complete withdrawal. Results: Were shown as mean ± SD. Mean EC-MPS dose: 840 mg/m2/day. Accumulative doses of steroids (mg/pat/mo) from 24 months before used EC-MPS: 1890 mg/pat/month and after 24 months: 560 mg/pat/month. Variation of steroid’s toxicity after and before used EC-MPS: Bone mineral density: OR: 4.6(IC 95% 3.4–6.4. Mean arterial pressure: OR, 2.4(IC95%1.93–3.03. Percentile of growth rate: OR 2.1(IC95%1.73–2.8). Mean number of relapsing episodes patient/year: Pre- EC-MPS 4.1(SD 1) Post-EC-MPS 1(SD 0.6) Wilcoxon matched-pairs signed-ranks test two-tailed P value is <0.0001, considered extremely significant.

Conclusions: Post-EC-MPS the number of relapsing episodes decreased significantly Post EC-MPS the risk of develop adverse events in regard with use of steroids decreased significantly More patients need to be assessed so as to confirm these preliminary conclusions.

PS2-FRI-009

Proteinuria as primary symptom of lysosomal storage diseases: Fabry disease and nephrosialidosis

M. Bald* ¹, M. Holder¹, K. Timmermann¹, U. Helmchen², Y. Shibn³, T. Podskarbi³, H. E. Leichter¹

¹Pediatric Nephrology, Olgahospital, Stuttgart, Germany, ²Kidney Register, Institute for Pathology, University Hamburg, Hamburg, Germany, ³Laboratory for Metabolic Genetics, München, Germany

Lysosomal storage diseases are rare genetic disorders with accumulation of metabolic breakdown products in lysosomes due to an enzymatic defect. Although kidneys may be involved, renal symptoms occur normally in the later course of the diseases. We report about two patients in whom proteinuria was the presenting symptom.

An 11 year old boy presented with granulomatous lymphadenitis from which he recovered completely. Follow up urinalysis showed persistent microhematuria and moderate proteinuria (protein/creatinine ratio 1.8 g/g). He only complained about reduced sweating leading to heat intolerance. A kidney biopsy at the age of 16 years showed laminary bodies in the cytoplasm of the podocytes, typical for Fabry disease, a lysosomal storage disease with accumulation of globotriaosylceramid. Further work-up showed a reduced alpha-galactosidase in leucocytes [0.06 nmol/min/mg protein, normal 0.4–1.0] and a hemizygous mutation in the corresponding gene [transition c. 416 A>G].

A 5 year old girl presented with nephrotic range proteinuria (protein-creatinine ratio 2.7 g/g) and slightly decreased serum albumin (31 g/l) without edema. There were no other clinical symptoms or laboratory signs of an active glomerulonephritis. A kidney biopsy demonstrated severe foam cells formation in the podocytes, pathognomonic for lysosomal storage disease. An enzymatic examination showed decreased neuraminidase activity in the leucocytes [0.9 nmol/h/mg protein, normal 5–20] and elevated chitotriosidase in plasma [20.4 nmol/min/ml; normal <1.5]. Ophthalmologic examination showed minimal corneal opacity and a cherry-red spot. These results are diagnostic for nephrosialidosis.

Our two patients presented with moderate proteinuria. The kidney biopsy and enzymatic studies led to the diagnosis of rare lysosomal storage diseases: Fabry disease, which can be treated by enzyme replacement therapy and nephrosialidosis, for which no specific treatment is available.

PS2-FRI-014

SPP1 gene polymorphisms associated with nephrolithiasis in Turkish pediatric patients

G. Tekin¹, P. Ertan* ¹, G. Dinc Horasan², A. Berdeli³

¹Celal Bayar University, Department of Pediatric Nephrology, Manisa, Turkey, ²Celal Bayar University, Department of Public Health, Manisa, Turkey, ³Ege University, Department of Pediatrics, Molecular Medicine Laboratory, Izmir, Turkey

Osteopontin (OPN) is one of the glycosylated phosphoproteins synthesized in the kidney that can modulate nephrolithiasis. In this study we investigated the association between SPP1 gene polymorphisms and nephrolithiasis. Total of 65 pediatric patients (age range 4 to 210 months) and 50 healthy controls were enrolled. Two known polymorphisms of the SPP1 gene, c.240T > C and c.708C > T nucleotide substitutions, both of which were also known as synonymous aminoacid polymorphisms, D80D and A236A respectively, at SPP1 gene cDNA level were investigated. SPP1 gene polymorphism was evaluated using PCR-RFLP method. In c.240T > C polymorphism, C allele frequency (OR = 2.13; CI = 1.170–3.880; p = 0.013) and CC genotype distribution (OR = 2.946; CI = 0.832–10.431; p = 0.094) and in c.708C > T polymorphism T allele frequency (OR = 2.183; CI = 1.197–3.980; p = 0.011) and TT genotype distribution (OR = 3.056; CI = 0.861–10.839; p = 0.084) were found to be higher in the patient group. In conclusion, SPP1 polymorphisms were found to be associated with nephrolithiasis and it may be suggested that SPP1 gene polymorphism could be a useful marker for evaluation of the early genetic risk factor in childhood nephrolithiasis.

PS2-FRI-015

Clinical and genetic characteristics of primary hyperoxalurias type 1 in children

S. Papizh* ¹, L. Prikhodina¹, E. Zakharova², M. Nagel³

¹Research Institute of Pediatrics and Children surgery, Moscow, Russian Federation, ²Medical Genetics Research Center, Moscow, Russian Federation, ³Laboratory for molecular diagnostics, Weisswasser, Germany

Case 1: 5 years old boy, 1st product of nonconsanguineous marriage. At the age of 7 months first episode of stone rate, renal ultrasonography showed bilateral medullare nethrocalcinosis, grade 2. Blood electrolytes, acid-base composition was normal. Excretion of Ca, P, urate, glycerate was normal, GFR was 80 ml/min/1.73 m². There was high level of oxalate/creatinine (0,9–1.5 (N < 0,1 mmol/mmol)and glycolate/ creatinine (318,7 (N 28–12 mmol/mmol) ratios in his urine. Screening for 1,4,10 exone of AGXT gene revealed compound AGXT heterozygous mutation in 1 exon—c.155insC. The boy has been treated with high fluid intake (more 2.000 ml) and pyridoxine (12 mg/kg). On the last follow-up, at the age 6 years the boy has painful passage of stones, his GFR was 100 ml/min/1.73 m².

Case 2: Girl was born to nonconsanguineous parents. Nethrocalcinosis firstly revealed at the age of 4 years old. Clinical and biochemical blood test, electrolytes, acid-base status of blood were normal. Excretion of Ca, P, urate, glycerate were normal, cystine test—negative. Oxalate/creatinine ratios was elevated—1,7 (N < 0,1 mmol/mmol), X-ray showed Rg-positive stones in both kidney. Renal function was normal (GFR −90 ml/min/1.73 m²). Direct sequencing of oll exons of the AGXT gene identified the c.121G > A (pG41R) mutation in exon 1 and c.508G > A (pG170R) mutation in exone 4. The girl has been treated with high fluid intake (more 2.000 ml) and pyridoxine (10 mg/kg). On the last follow-up (1 year later), his GFR was 60 ml/min/1.73 m².

Collaboration with internet will allow to predict outcome of disease, efficiency of treatment with pyridoxine.

PS2-FRI-021

Brain tumor as a late outcome of a child with nephrotic syndrome—is it any association with mycophenolate mofetile?

N. Hooman* ¹, F. Hallaji², M. Mehrazma³

¹Department of Pediatric Nephrology, Ali-Asghar Children Hospital, Tehran University of Medical Science, Tehran, Iran, ²Department of Pediatric Radiology, Ali-Asghar Children Hospital, Tehran University of Medical Science,Tehran, Iran, ³Department of Pathology, Ali-Asghar Children Hospital, Tehran University of Medical Science,Tehran, Iran

Background and aim: The association of idiopathic nephrotic syndrome with lymphoma, colon carcinoma, or bronchogenic carcinoma has been reported. We presented a child with focal segmental sclerosis who lately presented with brain tumor eleven years after renal presentation.

Method and result: This was a 16- year old boy, presented with nephrotic syndrome since age 5-year. He was steroid responder at first but after subsequent relapses he became steroid dependent. Renal biopsy showed focal segmental glomerulosclerosis. Two years after presentation cyclosporine with dosage of 4 mg/kg /day was started and hypertension was controlled with enalapril, losartan, and atenolol. But after one year he had massive proteinuria (6 gr/day); therefore, Mycopheolate mofetile (700−100 mg/m2/day) was added to therapy and the full dosage was continued for 2 years and then tapered during another one year. The proteinuria gradually decreased to 1.6 gr /day while GFR was normal (100 ml/min/1.73 m²). Afterward, enalapril and losartan only continued for another one year that was discontinued by the patient. There years later he presented with a sense of electric shock on his right hand and felt numbness and weakness on the right arm. He had central facial palsy. Brain CT scan showed a large mass [Figure 1]. The mass was completely removed by surgery and the pathology was compatible with Glioblastoma multiform [Figure 2]. Standard chemotherapy and radiotherapy were started. searching literature we found that cyclosporin suppress the gene of glioblastoma so we suggest the other prescribed medication as responsible trigger.

Conclusion: The occurrence of brain tumor one decade after immunosuppressive therapy in this child might be a late sequel or the coincidence. This might be an alarm for using immunosuppressive more cautiously.

PS2-FRI-022

Elevated urinary vascular endothelial growth factor in nephrotic syndrome

S. Shalaby* ¹, H. Mohamed², R. Safar², S. Taha²

¹Department of pediatrics, College of Medicine, Taibah University, AL-Madinah AL-Munawrah, Kingdom Of Saudi Arabia, ²Department of pediatrics, Maternity and Children Hospital AL-Madinah AL-Munawrah, Kingdom Of Saudi Arabia

Aim: The aim of the study was to assess urine concentrations of vascular endothelial growth factor (uVEGF) in nephrotic syndrome children (NS) and to define further the involvement of VEGF in MCNS.

Methods: We examined 90 children (2_/16 years), allocated to three groups: group I: 30 children with the first NS onset, group II: 30 children with NS in relapse, group C: 30 healthy children. The NS patients were examined: (A) before treatment and (B) 4_/5 weeks after prednisone administration at a dose of 60 mg/m2/24 h. urinary VEGF (uVEGF) levels were determined using the immunoenzymatic ELISA method.

Results: Markedly increased urinary levels of VEGF (uVEGF) were detected in both groups of patients with the nephrotic syndrome (NS) (536.9 ± 30.5) and (447.6 ± 70.3) when compared with normal controls(104.6 ± 30.7) (p = <0.05). . The (uVEGF) levels correlated with the degree of proteinuria in patients with first onset(r = 0.71 and p = <0.05) and recurrent relapses patients (r = 0.63 and p = <0.05). Moreover, uVEGF levels were increased during the active phase and decreased as the patients went into remission. This may hypothetically be explained by two possibilities: Increases excretion of uVEGF might be related to a specific glomerular pathology and consequently have a pathophysiological role. Alternatively, uVEGF may be derived from the circulation and as such may be nothing more than a biomarker for proteinuria. Considering the strict correlation between uVEGF excretion and the albumin creatinine ratio, the second possibility appears more conceivable.

Conclusion: Therefore, increased levels of (uVEGF) in both groups of patients with the (NS) may be a coincidental finding which has no bearing on the pathophysiology of MCNS.

This work was financially supported and fully funded by the king Abdulaziz city for technology and researches, Kingdom of Saudi Arabia. Under Grant No. APP 52-28.

PS2-FRI-024

Atypical cases of Dent’s disease presenting as asymtomatic proteinuria and focal glomerulosclerosis and identification of new CLCN5 mutations

E. Ramos-Trujillo* ¹, H. Gonzalez-Acosta¹, J. Fons², G. Ariceta³, B. Valenciano⁴, M. Garcia-Ramirez⁵, R. L. Muley-Alonso⁶, J. Vara⁶, V. Garcia-Nieto⁷, F. Claverie-Martin¹

¹Unidad de Investigacion, Hospital Universitario N.S. de Candelaria, Santa Cruz de Tenerife, Spain, ²Hospital Clinic Universitari, Valencia, Spain, ³Hospital de Cruces, Baracaldo, Spain, ⁴Hospital Materno Insular, Las Palmas de Gran Canaria, Spain, ⁵Hospital Materno Infantil, Malaga, Spain, ⁶Hospital Universitario “12 de Octubre”, Madrid,Spain, ⁷Nefrologia Pediatrica, Hospital Universitario N.S. de Candelaria, Santa Cruz de Tenerife, Spain

Objectives and study: Dent’s disease is an X-linked renal tubulopathy characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, nephrolithiasis and progressive renal failure. Recently, it has been postulated that this disease is an under recognized cause of focal segmental glomerulosclerosis (FSGS). Two-thirds of the cases of Dent’s disease are associated with inactivating mutations in the CLCN5 gene and a few present mutations in OCRL1. Both genes encode proteins involved in the endocytic pathway for reabsortion of low-molecular-weight proteins in the proximal tubule. Here, we describe two atypical cases presenting with asymptomatic proteinuria. We also report six conventional cases and new mutations in CLCN5.

Patients and methods: Six patients had LMWP and nephrocalcinosis or nephrolithiasis, and three of them show hypercalciuria. The other two patients presented asymptomatic proteinuria, hypercalciuria and had biopsy evidence of FSGS. The CLCN5 gene of patients and relatives was analyzed by PCR amplification of the coding exons and their intronic flanking regions and DNA sequencing.

Results: CLCN5 mutations were detected in seven patients, including the two patients showing FSGS. Five mutations were new; missense mutations G65R and G466D, a nonsense mutation, Y164X, a complex allele (H107P and V108fsX135) and one frameshift mutation, 1248delT. The other two mutations detected, W22G and R704X, had been previously identified.

Conclusions: We have expanded the number of CLCN5 mutations identified in patients with Dent’s disease. Our results suggest that diagnosis of Dent’s disease should be considered in cases of unexplained proteinuria and idiopathic focal glomerulosclerosis.

This work was supported by grant PI09/91009 from Fondo de Investigación Sanitaria (Spain). Our group is part of Renaltube (https://doi.org/www.renaltube.com).

PS2-FRI-025

Vascular endothelial growth factor is not operating as a vascular permeability factors in nephrotic syndrome

S. Shalaby* ¹, H. Mohamed², R. Safar², S. Taha³

¹Department of pediatrics, College of Medicine, Taibah University AL-Madinah AL-Munawrah, Kingdom Of Saudi Arabia, ²Department of pediatrics, Maternity and Children Hospital AL-Madinah AL-Munawrah, Kingdom Of Saudi Arabia, ³Department of Clinical Pathology, King Fahad Hospital, AL-Madinah AL-Munawrah, Kingdom Of Saudi Arabia

Aim: The aim of the study was to assess plasma concentrations of vascular endothelial growth factor (pVEGF) in nephrotic syndrome children (NS) and to define further the involvement of VEGF in pathogenesis of proteinuria.

Methods: This is a across-sectional prospective. We recruited 90 children (2_/16 years), divided into three groups: group I: 30 children with the first NS onset, group II: 30 children with NS in relapse, group C: 30 healthy children.

The NS patients were examined: (A) before treatment and (B) 4–5 weeks after prednisone administration at a dose of 60 mg/m2/24 h. plasma VEGF (pVEGF) levels were determined using the immunoenzymatic ELISA method.

Results: There was no significant difference between any of the study groups or even within groups. In group I plasma VEGF levels both before (222.0 ± 19.5) and after (134.6 ± 30.3) steroid therapy were not significantly different from control group (118.4 ± 22.9) (p > 0.05). In group II, there were no significant differences either before (229.4 ± 13.5) or after (138.2 ± 11.1) steroid therapy (p > .05), or in comparison to the control group (118.4 ± 22.9) (p > 0.05). (pVEGF) levels were not correlated with the degree of proteinuria in patients with NS (r = 0.13 and p=>0.05). CONCLUSION: The current results does not support the idea that VEGF is operating as a vascular permeability factors in nephrotic syndrome.

This work was financially supported and fully funded by the king Abdulaziz city for technology and researches, Kingdom of Saudi Arabia. Under Grant No. APP 52-28.

PS2-FRI-028

Anti-factor H antibodies in Japanese children with atypical hemolytic uremic syndrome

M. Nishimura* ¹, K. Maekawa¹, F. Kawashima¹, N. Takagi¹, J. Sawaki¹, C. Takahashi¹, H. Mae¹, M. Hattori¹, T. Tanizawa¹

¹Department of Pediatrics, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

Hemolytic Uremic Syndrome (HUS) is classified into typical HUS and atypical HUS (aHUS). In many cases, aHUS is sporadic or familial, and has poor prognosis. About 50% of aHUS have mutations of the complement regulatory proteins factor H (CFH), membrane cofactor protein (MCP) or factor I (CFI). aHUS associated with anti-CFH antibodies (ab) accounts for 6-11% in reported literatures. Here we report our case of aHUS associated with anti-CFH-ab, and show clinical features in 14 cases of Japanese aHUS children.

Objectives: We report our case of aHUS associated with anti-CFH-ab, and show clinical features in 14 cases of Japanese aHUS children.

Materials and methods: 14 cases with Japanese aHUS children were enrolled. Anti-CFH ab was detected by an ELISA method. Positive samples were reconfirmed by Dr MA Dragon-Durey.Anti-CFH ab was positive in 4 patients, whereas others were negative.

Results: We examined anti-CFH-ab in 14 Japanese aHUS children, 4 children (29%) had high titer. All 4 patients of positive anti-CFH-ab needed intensive immunosuppressive therapy after plasmapheresis. There was no recurrence of aHUS after treatment. Examining anti CFH-ab needs to be considered in aHUS patients for its treatment and prognosis.

Conclusion: The examination of Anti CFH-ab was important role for treatment and diagnosis in aHUS children.

PS2-FRI-029

Renal function and hypercalciuria in children affected by osteogenesis imperfecta

M. Brugnara* ¹, F. Doro¹, E. Monti¹, G. Morandi¹, E. Maines¹, F. Antoniazzi¹

¹Department of Life and Reproduction Sciences, Paediatric Clinic, University of Verona, Verona, Italy

Osteogenesis Imperfecta (OI) is a group of inherited disorders of connective tissue characterized by bone fragility, laxity of ligaments, blue sclera and short stature. Hypercalciuria is a condition characterized by an urinary calcium excretion >4 mg/kg/die or urinary Ca/Cr ratio >0,21. The aim of this study is to observe the incidence of hypercalciuria adn related problems among patients affected by OI. We also want to verify the presence of any kidney damage related with the increased urinary calcium or with the treatment with bisphosphonates.

We have recruited 36 patients, followed at our clinic, treated with biphosphonates. We collected, in two times (T0–T1), auxological, clinical and laboratory parameters. All patients performed an abdominal ultrasound. In T0 we have investigated the patients’ alimentary habits with a talk and a questionnaire. Afterwards we have normalized the patients’ diet in the sodium and calcium engagement, as from LARN indications.

The average calcium intake with diet in these patients is lower than the levels indicated by LARN normalized for age. Through urinary Ca/Cr ratio we have identified 11 hypercalciuric patients in T0, 15 in T1. We didn’t found any alterations in kidney function both in biochemical and in imaging data. But estimating the urinary calcium in mg/kg/die in T1, we’ve also observed that hypercalciuric patients were only 6.

We haven’t found correlation between hypercalciuria and severity of OI. Urinary Ca/Cr ratio is not specific enough to detect hypercalciuria in our patients, maybe because of low creatinine levels. This population needs a dietary integration with Calcium and Vitamin D. Hypercalciuria and the treatment with bisphosphonates do not cause any significant kidney alteration. Next studies with DXA are going to make a better evaluation of the influence of hypercalciuria on bones of patients affected by OI.

PS2-FRI-036

The renin-angiontensin-aldosterone-system (RAAS) blockers in diabetic nephropathy (DN)

N. Bánki* ¹, L. Wagner², Á. Vér³, A. Prokai¹, M. Rosta¹, Á. Vannay⁴, R. Gellai¹, A. Szabó¹, T. Tulassay^1,4, A. Fekete¹

¹1st Department of Pediatrics, Semmelweis University, Budapeat, Hungary, ²Department of Transplant Surgery, Semmelweis Univerity, Budapest, Hungary, ³Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary, ⁴Research Laboratory of Paediatrics and Nephrology at the Hungarian Academy of Sciences, Budapest, Hungary

Objectives and study: Renal RAAS is clearly activated in diabetes, which is the main cause of end-stage renal failure. Previously in a rat model of DN we found impaired renal function parallel with elevated expression and translocation of the renal Na/K ATPase (NKA). Heat-shock protein (HSP) 72 stabilized membrane associated NKA and preserved enzyme function. Here, we analyze the effect of various RAAS inhibitors on diabetes or hyperglycemia induced renal damage.

Methods: In vivo—Diabetes was induced in male Wistar rats with iv. Streptozotocin After 5 weeks of diabetes rats were treated daily with ACE inhibitor enalapril, ARB losartan and aldosteron antagonists spironolactone and eplerenone for 2 weeks p.o. Vehicle-treated diabetic, and treated non-diabetic animals served as controls (n = 6/group). Renal histology, kidney function, protein levels and intrarenal localization of NKA and HSP72 were evaluated. In vitro—HK-2 cells were cultured under 5 mM (C) and 35 mM (G) glucose concentrations and in 35 mM mannitol (M). G cells were treated with the same RAAS blockers for 72 hours. NKA and HSP72 protein levels were measured.

Results: Diabetes resulted in impaired renal histological and functional parameters, elevated and translocated renal NKA and HSP72. RAAS inhibitors ameliorated histological damage, while kidney function was mostly preserved by aldosterone antagonists. Each RAAS treatment -except enalapril—lowered renal NKA and HSP72 and prevented NKA translocation. Hyperglycemia induced elevation of tubular NKA was decreased by each treatment, except losartan.

Conclusion: Aldosteron antagonists, even in monotherapy might be beneficial in the treatment of DN beside ACE inhibitors and ARBs. RAAS inhibitors might help to stabilize NKA and thereby sodium homeostasis, which could be an additional explanation for their renoprotective effect. Supported by grants Pfizer, ETT, OTKA, Bolyai, TÁMOP, Baross.

PS2-FRI-044

Ciliogenesis in human kidneys during development and post-natal life

M. Saraga-Babić* ¹, K. Vukojević¹, I. Bočina², K. Drnasin³, M. Saraga⁴

¹School of Medicine, University of Split, Split, Croatia, ²Department of Biology, University of Split, Split, Croatia, ³Paediatric Outpatient Clinic, Solin, Croatia, ⁴Department of Paediatrics, University Hospital in Split, Split, Croatia

Objectives and study: Development of primary cilia (ciliogenesis) and its relationship to processes of cell proliferation and differentiation, apico-basal cell polarity and tubular lumen formation were analyzed in embryonic, fetal and post-natal human kidneys. Investigations on normal kidney ciliogenesis are important because alterations in function and structure of primary cilia might be associated with group of disturbances called ciliopathies.

Methods: Appearance and lengthening of primary cilia, as well as proliferation and maturation of kidney cells were analyzed in paraffin kidney sections of 10 human conceptuses 6–22 week old and in 5-yaer post-natal kidney. Electron microscopy, immunohistochemical and double immunofluorescent techniques to α-tubulin, Oct-4 and Ki-67 markers were used.

Results: During development, intense cell proliferation characterized immature forms of nephrons and ampullae, while it gradually decreased with advancement of nephron and collecting system maturation. Typical primary cilia, containing 9 + 0 microtubular pairs, appeared on the surfaces of non-proliferating cells in developing nephrons, gradually increased in length from 0.59 μm in renal vesicle stage to 0.81 μm in S-forms of nephrons, and finally to 3.04 μm in mature fetal and post-natal nephrons. In the collecting tubules, their length increased from 0.59 μm in ampullae to 1.28 μm in post-natal kidney. Mesenchymal to epithelial transformation of kidney cells was characterized by appearance of apico-basal polarity, gap junctions and typical epithelial cellular connections, followed by the first lumen formation at the renal vesicle stage. Increase in Oct-4 expression was associated with the onset of kidney cell differentiation in developing and post-natal kidneys.

Conclusions: Our data indicate importance of proper primary cilia development and lengthening for establishment of fetal and postnatal kidney function, and Oct-4 protein expression for normal differentiation of kidney cells during nephrogenesis. Appearance of apico-basal cell polarity and gap junction seems to be a pre-requisite for normal lumen formation and tubular morphogenesis.

PS2-FRI-045

Bardet-Biedl Syndrome: two cases and review of the literature

C. Zeybek¹, T. Mumcuoğlu², D. Ö. Hacıhamdioğlu¹, S. Kalman¹, E. Demirkaya¹, F. Gök* ¹

¹Gülhane Military Medical Academy Pediatric Nephrology Department, Ankara, Turkey, ²Gülhane Military Medical Academy Ophtalmology Department, Ankara, Turkey

Bardet-Biedl Syndrome (BBS) is a rare, genetically heterogeneous ciliopathy characterized by features of early-onset obesity, rod-cone dystrophy, polydactyly, renal malformations, hypogenitalism and cognitive impairment. We report here two cases presenting with findings of laryngeal web, posterior urethral valve and nephrotic range proteinuria.

PS2-FRI-046

Reproductive health of patients 14–35 years with steroid-sensitive nephrotic syndrome

I.V. Ivashchenko¹, G.F. Kutusheva¹, N.D. Savenkova* ¹

¹Saint-Petersburg Pediatric Medical Academy, Saint-Petersburg, Russian Federation

Background: The purpose of the research was to study reproductive health of girls with Steroid-sensitive Nephrotic syndrome (SSNS) who received standard glucocorticoid and cytostatic therapy (chlorambucil and cyclosporin) in childhood.

Patients and methods: The aim of a study was a long-term follow-up reproductive health of 30 patients with SSNS in age from 14 to 35 years receiving glucocorticoid and cytostatic therapy. SSNS is diagnosed in children with nephrotic syndrome, normal renal function, steroid responsiveness without biopsy.

Results: In 30 patients with SSNS who were taken ill in neutral and before puberty received isolated prednisolone therapy (23), combined by prednisolone and chlorambucil or cyclosporin (7). Glomerular Filtration Rate (creatinin clearance method) is normal in all 30 patients. Among the 30 patients with SSNS who were examined in long-term remission for 2–33 years, middle age of the beginning of menstruations makes 13 ± 0,4 years, regular menstrual cycles occurred. 30 patients with SSNS had normal sexual development. The 30 patients in long-term remission SSNS had regular menstrual cycles.

Of the 21 patients of childbearing age with a long-term remission SSNS, 8 (24,6 ± 3,80 years) reported 11 normal ran through pregnancy and childbirth, culminating in the birth of live full-term infants with no relapse of SSNS.

The weight of a body of 11 newborns made from 2880 g to 3700 g and averaged 3393,6 ± 240,3 g, the length of a body of newborns from 48 cm to 53 cm and averaged 51,3 ± 1,6 cm.

Conclusion: Reproductive health in 30 patients with SSNS in age from 14 to 35 years receiving glucocorticoid and cytostatic therapy is normal.

PS2-FRI-047

Response to steroids in early onset nephrotic syndrome

B. Aoun* ¹, S. Sanjad², H. Fakhoury², F. Shatila¹, T. Ulinski³

¹Rafik Hariri University Hospital, Beirut, Lebanon, ²American University Hospital of Beirut, Lebanon, ³Armand Trousseau University Hospital, Paris, France

The treatment of congenital nephrotic syndrome (CNS) is considered a challange for physician secondary to the presence of hereditary forms such as podocin, nephrin and other forms of mutation that are resistant to treatment. Despite being resistance to usual treatment, a trial by steroid should be considered irrespectively of the histological lesions. We reported two cases of nephrotic syndrome before the age of one year who was steroid sensitive. Case1, a 7 month old male presented with generalized edema, investigations showed normal kidney function, with biological alterations (total serum protein (TSP) of 32 g/l, albumin of 20 g/ and 24 hours urine collection showed proteinuria of 5 g/L) all other secondary causes of nephrotic syndrome were excluded. Kidney biopsy showed focal segmental sclerosis, symptomatic treatment was started (Albumin perfusion, anticoagulation), steroids were started (60 mg/kg/m2) and 8 days later the patient was in remission. Case 2, an 8 month old female with myelomeningocele admitted for progressive generalized edema, and investigations showed normal kidney function with a creatinine of 0.3 mg/dl, and a TSP of 40 g/l, albumin of 16 g/l, and the 24 hours urine collection for protein (6 g/l). Also all other secondary causes of nephrotic syndrome were excluded like syphilis, HIV, toxoplasmosis and Hepatitis B. Kidney biopsy showed lesion typical to those seen in CNS finnish type (irregularly dilated dilated proximal and distal tubules with increased number of cytoplasmic vacuoles filled with colloid like material) symptomatic treatment was started by albumin perfusion, and steroids orally.2 weeks later patient was in remisson. In conclusion despite the high resistance rate to treatment, several patients do respond to steroids as seen in our cases.

PS2-FRI-050

Except for Alport syndrome and thin basement membrane nephropathy, children with nephrotic syndrome have thinnest glomerular basement membrane

M.C.T.T. Gramberg* ¹, K. Grunberg², J.A.E. van Wijk¹

¹Dept of pediatric nephrology, VUMC Amsterdam, The Netherlands, ²Dept of pathology, VUMC Amsterdam, The Netherlands

Background: Normal values for glomerular basement membrane (GBM) in children are not exactly known. Values differ with age and method of measurement. Measuring GBM thickness is not always performed nor standardized in each biopsy and does not always contribute to the diagnosis. Correlating GBM thickness with clinical parameters may give a more accurate diagnosis in children with nephropathy.

Methods: We studied thin needle renal biopsy data from 472 children (years 1992 to 2010), aging 4 days till 18 years (mean age 9 years). A standardised measurement protocol for GBM thickness was developed. Three EM pictures were selected: GBM thickness in every glomerular loop was measured at five equally distributed points. The arithmetic mean was calculated for 281 patients. From 254 patients both GBM measurements and clinical parameters were present. Five diagnosis groups were classified: basement membrane nephropathy (BMN, including TBMN and Alport Syndrome n = 35), nephrotic syndrome (NS n = 107), mesangial proliferative glomerular disorders (MPG n = 22), IgA nephropathy (IgANP n = 44) and nephropathy otherwise specified (NOS n = 72). Linear regression analysis assessed correlation between the different diagnosis groups and mean GBM thickness.

Results: Mean GBM thickness results were as follows: BMN 258 nm, NS 304 nm, MPG 312 nm, IgANP 321 nm and NOS 333 nm. As expected BMN patients had significant lowest GBM thickness. After that NS had the lowest GBM thickness of all glomerular disorders, CONCLUSION: With a standardised method for measuring GBM thickness we compared GBM in different diagnostic entities. After TBM, NS patients had lowest GBM thickness. Refined analysis with single aspects of clinical data will be necessary.

PS2-FRI-052

Preserved slit diaphragm morphology in Finnish type congenital nephrotic syndrome

B. Eneman* ^1,2, K. Peeters², B. Van den Heuvel², E. Lerut³, E. Levtchenko^1,2

¹Department of child nephrology U.Z. Leuven, Belgium, ²Laboratory of paediatrics K.U. Leuven, Belgium, ³Department anatomopathology U.Z. Leuven, Belgium

Introduction: Congenital nephrotic syndrome (CNS) of the Finnish type is caused by bi-allelic mutations in the NPHS1 gene encoding for nephrin. In patients with CNS due to homozygous Fin-major mutations, the absence of slit-diaphragms (SD) on electron microscopy (EM) was demonstrated. We present a patient with CNS due to a homozygous amino acid deletion in NPHS1, who showed atypical renal histology with mesangial hypercellularity and preserved SD on EM.

CASE: A female patient presented shortly after birth with severe proteinuria, hypoalbuminemia and peripheral edema, pointing to the diagnosis of CNS.

A kidney biopsy was performed at 3.5 months of age and demonstrated diffusely increased mesangial cellularity. EM demonstrated partial foot process effacement. In the regions with normal foot process morphology preserved SD were visible.

Analysis of the NPHS1 gene demonstrated a homozygous c.514_516ACC (p.t172del) mutation, previously described in two non-Finnish patients with CNS. Both parents and a healthy sibling of our patient were carriers of the mutation.

At 1 year of age a nephrectomy of the right kidney was performed to reduce proteinuria. Surprisingly, the histological examination of the kidney showed normal mesangial cellularity. No tubular dilatations characteristic for CNS of the Finnish type were observed. SD were still present in podocytes with preserved foot morphology.

Conclusion: In this case, a homozygous deletion of threonine at position 172 in the NPHS1 gene leads to the clinical phenotype of a Finnish type CNS, despite preserved SD morphology. This mutation possibly leads to an aberrant function of nephrin without causing evident (ultra)structural changes. Podocyte cell lines were obtained from this kidney specimen for studying the mechanisms of podocyte dysfunction. The results of these studies will bring new insights on molecular pathogenesis of CNS.

PS2-FRI-060

A diagnostic dilemma: food induced pulmonary renal syndrome with hemihypertrophy

S. Yavuz* ¹, A. K. Bayazıt¹, M. Yılmaz², G. Gonlusen³, A. Anarat¹

¹Cukurova University, Pediatric Nephrology, Adana, Turkey, ²Cukurova University, Pediatric Allergy and immunology, Adana, Turkey, ³Cukurova University, Pathology, Adana, Turkey

Crescentic glomerulonephritis is also known as rapidly progressive glomerulonephritis. Pulmonary-renal syndrome represents a combination of diffuse alveolar hemorrhage together with crescentic glomerulonephritis. It is very rare but potentially fatal. Vast majority of cases are ANCA related. In this case we report a hemihypertrophic eight-year-old boy with a clinical picture of food induced pulmonary renal syndrome. Although clinical manifestations were compatible with Churg-Strauss syndrome, Good-Pasture’s syndrome was not properly excluded because of anti-GBM positivity. This is the first case resembling food induced pulmonary haemorrhage together with crescentic glomerulonephritis and also with hemihypertrophy.

PS2-FRI-064

Prothrombotic DNA polymorphisms in children with glomerulonephritis from north-western Russia

K.A Papayan¹, S.I. Kapustin², N. D. Savenkova* ¹

¹Department of pediatric nephrology, State Pediatric Medical Academy, Saint-Petersburg, Russian Federation, ²Russian Research Institute of Haematology and Transfusiology, Saint-Petersburg, Russian Federation

The aim: To investigate the features of allele and genotype distributions for several prothrombotic DNA polymorphisms in children with glomerulonephritis (GN).

Patients and methods: The group of 75 children with GN (55—primary, or idiopathic; 20—secondary to vasculitis) from 5 to 18 years of old was analyzed. The control group consisted of 228 age- and sex-matched healthy controls (HC). All the persons included in the study were originating from the North-Western region. Prothrombotic DNA polymorphisms in the genes coding for coagulation factor V (G1691A, FV Leiden mutation), factor II (prothrombin G20210A), factor I β-subunit (fibrinogen G − 455A), plasminogen activator inhibitor type I (PAI-1 −675 4G/5G), methylenetetrahydrofolate reductase (MTHFR C677T) and glycoprotein IIIa (GpIIIa T1565C) were discriminated by polymerase chain reaction and subsequent restriction digest (PCR-RFLP). The differences in allele genotype distributions between groups were estimated by Fisher’s exact test.

Results: The homozygous GpIIIa 1565CC genotype was much more prevalent in the patients (5,3% vs. 0,9% in the control group, OR = 6,4; p = 0,035). The frequencies of MTHFR 677TT and fibrinogen −455AA genotypes were decreased in GN group when compared to HC (4,0% vs. 10,1%, OR = 0,4; p = 0,15 and 2,7% vs. 7,9%, OR = 0,3; p = 0,18, respectively). The 4G/4G variant of PAI-1 gene was more frequently seen in children with primary GN (40,0% vs. 25,0% in patients with secondary GN, OR = 2,0; p = 0,28). At the same time, the homozygous genotypes of GpIIIa (1565CC) and factor I (−455AA) were more prevalent in children with secondary GN when compared to the group of patients with primary GN (15,0% vs. 1,8%, OR = 9,5; p = 0,056 and 10,0% vs. 0,0%, OR = 15,0; p = 0,069, respectively).

Conclusions: The observed results suggest the different mechanisms of hypercoagulability formation in children with primary and secondary GN.

PS2-FRI-065

Changes of ciliogenesis in congenital nephrotic syndrome of the Finnish type

M. Saraga* ¹, K. Vukojević², V. Krželj¹, Z. Puretić³, I. Bočina⁴, M. Glavina Durdov⁵, B. Dworniczak⁶, S. Weber⁷, M. Saraga-Babić²

¹Department of Paediatrics, University Hospital in Split, Split, Croatia, ²Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Split, Croatia, ³Department of Dialysis, University Hospital Centre Zagreb, Zagreb, Croatia, ⁴Department of Biology, University of Split, Split, Croatia, ⁵Department of Pathology, University Hospital in Split, Split, Croatia, ⁶Department of Human Genetics, University of Münster, Münster, Germany, ⁷Division of Pediatric Nephrology, University Children’s Hospital Essen, Essen, Germany

Congenital nephrotic syndrome of the Finnish type (CNF) is characterized by nephrotic proteinuria, hypoproteinemia, hyperlypidemia and edema, manifesting in the first 3 months of life, caused by mutations of NPHS1 gene, encoding nephrin (OMIM 602716). In the first male patient with proven CNF in Croatia, ciliogenesis and differentiation of kidney cells in nephrotic kidneys were analyzed and compared to normal post-natal kidneys.

Methods: Besides clinical examination of CNF patient, we made analysis of urine and urine culture, biochemical analysis of blood, blood culture, genetic analyses, and patohistological examination of the kidneys. Electron microscopy (EM) and immunohistochemical techniques using anti-tubulin and anti-Oct-4 antibodies were used in kidney tissues of the patient and normal kidneys.

Results: Clinical and laboratory signs of CNF were observed at birth. Ultrasonographic findings of patient’s kidneys were typical for CNF. Patient received supplementary therapy. Genetic screening identified a homozygous missense mutation (c.1096A > C;p.Ser366Arg) in NPHS1 as underlying cause of the disease. Patient underwent nephrectomy at the ages of 12 and 22 months, respectively, and CAPD was initiated. Histopathological findings included glomerulopathy and microcistically dilated tubules, while electron microscopy disclosed loss of podocyte processes. Immunohistochemically, α-tubulin staining of normal kidneys showed 3.04 μm long cilia on surface of each nephron tubular cells and 1.28 μm long in collecting tubules. In CNF, no primary cilia were found in tubular microcysts, while extremely long or dysmorphic cilia (8.41 μm long) characterized partly dilated nephrons and collecting tubules (9.59 μm). In comparison to normal kidneys, nephrotic kidneys showed changed in expression pattern Oct-4 marker of differentiation.

Conclusions: In nephrotic kidneys, disturbed ciliogenesis and cell differentiation was associated with microcyst formation, and with abnormal morphogenesis and maturation of nephrons and collecting system. In addition to genetic mutation of nephrin, CNF kidneys were characterized by ciliopathic changes.

PS2-FRI-067

A boy with Dent-2 disease

K. Vrljičak* ¹, D. Batinić¹, D. Milošević¹, Lj. Nižić-Stančin¹, M. Ludwig²

¹Division of Nephrology, Department of Pediatrics, University Hospital Centre Zagreb, Zagreb, Croatia, ²Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany

Objectives and study: Dent-2 disease is an X-linked tubulopathy associated with mutations in OCRL gene. It is characterized by low-molecular weight proteinuria, hypercalciuria, nephrolithiasis/nephrocalcinosis and progressive renal failure. This is a case report.

Methods and results: Patient was admitted at the age of 8 months because of persistent proteinuria and hematuria after urinary tract infection. Hypercalciuria up to 8.29 mg/kg/day and proteinuria up to 2.46 g/dU were found. At the age of 17 months calciuria was 5.17 mg/kg/day so we started treatment with amiloride, hydrochlorthiazide and citrate and got a good therapeutic response in reducing calciuria. At last control (age 46 months) calciuria was 1.89 mg/kg/day. We will consider the introduction of ACE inhibitors. OCRL mutation in exon 4 (c.166_167 del TT p.L56D, fs X57) was detected. The mutation was previously published once by Shrimpton et al. Patient’s mother is a carrier of that mutation. Renal scintigraphy showed a symmetrical tubular damage. Renal biopsy revealed normal glomeruli and interstitium was only at two places permeated by abundant connective tissue. Creatinine, bicarbonate and serum electrolyte levels were normal. He had no glycosuria or aminoaciduria. Psychological testing at 3 years recorded appropriate mental development. Renal ultrasound, ophthalmologic and cardiologic examination remained normal till date.

Conclusions: The diagnosis was established in a very young patient so it is possible that the other phenotypic features manifest later in life. Dent-2 patients may have some extra-renal symptoms of Lowe syndrome, such as peripheral cataracts, mental impairment, stunted growth or elevation of creatinine kinase/lactate dehydrogenase. Except shorter stature (5th centile for age), our patient has no prominent extra-renal symptoms. Renal biopsy did not reveal the changes that have been described by some authors.

PS2-FRI-071

Genotype-phenotype correlation in pediatric patients with Familial Mediterrenean Fever

G. Ozcelik* ¹, N. Akinci¹, A. Caglar¹, H. Gencer¹, N. Urganci¹

¹Sisli Etfal Education and Research Hospital, Department of Pediatric, Istanbul, Turkey

Aim: Familial Mediterrenean Fever (FMF) gene has been cloned to chromosome 16p, 50 different mutations have been identified. Ethnicity and environmental factors can change phenotyic effects of mutations. We aimed to evaluate genotype-phenotype correlation in our patients.

Material and methods: We enrolled 81 FMF patients retrospectively, analyzed clinical and genetic features. Tel Hashomer criteria were used at diagnosis of FMF. The severity of FMF was assessed by PRAS pediatric modified score.

Results: Mean age of patients was 12,68 ± 3,39 years with a male:female ratio of 1.3:1. Mean age at onset of the symptoms was 6.92 ± 3.96, time from symtoms to diagnose was 2.34 ± 2.75 years. Clinical features included abdominal pain(98.8%), arthralgia(80.2%), chest pain(43.2%), myalgia(27,2%), arthritis(21%), erysipelas-like erythema(14.8%), scrotal edema(9.9%). Mean of frequency of attacks was 2.5 ± 0.3/year, mean duration of attacks was 41.5 ± 29.2 hours. The disease severity levels were mild at 32.1%, intermediate at 63%, severe at 4.9% of cases. Seven different MEFV gene mutations were found in 56 patients and 94 alleles, M694V was the most frequent mutation. Mutations were heterozygous in 27.2%, homozygous other than M694V in 23.5%, homozygous M694V in 18.5% patients. There was no difference among groups at frequency of abdominal pain, chest pain, arthralgia, myalgia and erysipelas-like lesions. However the patients with M694V/M694V genotype had higher frequencies of arthritis, amyloidosis and had high severity score. Patients with all homozygous mutations have higher frequecies scrotal edema than other patients. There was no difference among groups at response to treatment, age at onset of symptoms, age at diagnosis, time of diagnostic delay, duration of attack and frequency of attack.

Conclusions: MEFV mutation has been used supportive and complementary to diagnosis of FMF. The clinician has to decide the treatment and follow-up according to the clinical features and mutations of FMF. It should be kept in mind that amyloidosis seen more frequently in patient with M694V genotype.

PS2-FRI-073

Several genetic aberrations in different complement genes in a patient with MPGNII

D. Westra* ¹, H. van der Deure² , E. Volokhina¹, L. van den Heuvel^1,3, N. van de Kar¹

¹Dept. of Paediatric Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, ²Dept. of Paediatrics, Deventer Hospital, Deventer, The Netherlands, ³Dept. of Paediatrics, University Hospital Leuven, Leuven, Belgium

Objectives and study: Membranoproliferative glomerulonephritis type II (MPGNII) is characterized by onset of hematuria and/or proteinuria, acute nephritic or nephrotic syndrome. The exact pathogenesis is still not known, but there is an involvement of the complement system. In some patients, C3-nephritic factor (C3NeF), which stabilizes the C3 convertase C3bBb, or mutations in Complement Factor H are found. Here, we identify aberrations in genes encoding proteins of the alternative pathway or the membrane attack complex (MAC) in a MPGN II patient with low C3 values.

Methods: In one MPGNII patient, mutational screening was performed in alternative pathway genes CFH, CFI, MCP, CFHR5, C3, CFB, and CFD, and MAC genes C8A, C8B, and C9. Potential pathogenicity of genetic alterations was checked in literature, evolutionary conservation, and in silico mutation prediction programs.

Results: The male patient presented at age six with hematuria without other symptoms. C3 values were low (<0,5 mg/l; normal values: 0.9–1.8 g/l), indicating ungoing activation of the alternative complement pathway. MPGN II was identified in a renal biopsy. The patient is C3NeF positive, but αFH negative; no drusen are present, yet. A genetic aberration was found in CFD (A41P), in C3 (K155Q), and in C8A (A221E). Prediction models for structural influence of the mutations will be displayed. Family screening showed that only the MPGN II patient carried all three genetic variations; family members were not screened for C3NeF, yet.

Conclusion: In our MPGNII patient, three potentially pathogenic aberrations are found in complement genes of the alternative pathway and MAC, which have not been associated with MPGNII, previously. Healthy family members carried only one or two of these variations. This indicates that, next to C3NeF, a combination of genetic defects in the complement system might be needed to display the disease.

PS2-FRI-075

Nephrocalcinosis associated with Schimke immuno-osseous dysplasia

S. Yavuz* ¹, A. K. Bayazıt¹, A. Anarat¹

¹Cukurova University, School of Medicine, Department of Pediatric Nephrology, Adana, Turkey

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystem disorder consisting of characteristic phenotype, spondyloepiphyseal dysplasia, defective T-cell-mediated immunity, and progressive renal disease. The most common renal pathology is focal segmental glomerulosclerosis and prognosis is mainly due to the renal involvement. Nephrocalcinosis is uncommon in childhood and has not ever been identified in SIOD before. Here we report the first case of a pediatric patient having typical features of SIOD together with nephrocalcinosis. This case re-emphasizes that SIOD should be considered in children presenting with skeletal dysplasia and renal disturbances. Routine ultrasonographic examination of those patients is recommended to display unusual renal abnormalities.

PS2-FRI-079

Thyroid function in children with steroid-sensitive nephrotic syndrome

M.M. Smirnova¹, L.W. Tyrtova², N.D. Savenkova* ¹

¹Saint-Petersburg State Pediatric Medical Academy, Department of pediatric nephrology, Saint-Petersburg, Russian Federation, ²Saint-Petersburg State Pediatric Medical Academy, Department of pediatry, Saint-Petersburg, Russian Federation

Background: The purpose of the research was to study thyroid function in children with steroid-sensitive nephrotic syndrome (SSNS) in relapse and remission.

Patients and methods: the study includes 35 children with SSNS (range 2–17 years). Thyroid-stimulating hormone (TSH), total thyroxine (T4), free thyroxine (FT4), triiodothyronine (T3) were assayed by enzyme-linked immunosorbent assay.

Results: Eight patients with SSNS in relapse had proteinuria ranged from 2,03 to 6,64 g/m2/24h (3,93 ± 1,64), serum total protein 47,5 ± 5,83 g/l, albumin 18,76 ± 4,64 g/l, cholesterol 10,04 ± 4,11 mmol/l, low-density lipoprotein (LDL) 81,5 ± 22,26 U/l, edema and normal glomerular filtration rate. All patients received corticosteriod treatment. Four patients had elevated TSH levels (7,71 ± 3,02 μIU/ml). Three patients among them had normal T4 and FT4 levels (96,7 ± 32,48 nmol/l and 16,9 ± 2,82 pmol/l respectively), latent hypothyroidism was diagnosed. One of four patients with severe hypoalbuminaemia (11,4 g/l) had the reduction of T4 and FT4.

In remission SSNS were examined 32 patients. Part of patients received supporting prednisolone therapy. Serum protein level was 68,53 ± 7,11 g/L, albumin - 33,82 ± 3,84 g/l, cholesterol −5,46 ± 1,52 mmol/l, LDL - 46,31 ± 11,28 U/l. All patients had TSH, T4 and FT4 within normal range (2,71 ± 0,84 μIU/ml, 110,92 ± 14,61 nmol/l and 16,38 ± 4,19 pmol/l respectively), including 3 children with hypothyroidism in the relapse SSNS.

The mean serum T4 concentration in relapse was lower (p < 0,05) and TSH higher (p < 0,05) than in remission of SSNS. Serum T4 showed a moderate correlation with the serum albumin (r = 0,45) and cholesterol (r = −0,47). The daily proteinuria showed a moderate negative correlation with the serum T4 (r = −0,49) and FT4 (r = −0,55).

Conclusion: The hypothyroidism in the relapse of SSNS was revealed in 4 children. The thyroid function in remission was normal in all patients.

PS2-FRI-081

Bone mineral density in adolescents with chronic kidney disease

J. Slavicek* ¹, Z. Puretic¹, Z. Mustapic¹, S. Cvijetic²

¹Departmen of nephrology, dialysis, transplantation, UHC Zagreb, Croatia, ²Institute for Medical Research and Occupational Health, Zagreb, Croatia

The aim of this follow-up study was to analyze the change of bone mineral density (BMD) in adolescents with chronic renal failure and to determine the influence of height, weight, and bone size on bone density. 30 patients aged 13,5 ± 3.5 ys were included. Serum calcium, phosphorus, and PTH were measured. BMD was measured by DXA.The mean time between baseline and follow up measurements was 15,7 months. Despite significant increase of weight and height in all participants, anthropometric variables were below one SD from reference values in both measurements.(Z value <−1). After correction for height and weight, increase of BMAD between two measurements was not significant. It is necessary to correct BMD for height and weight in children with CKD, due to their retarded growth velocity.

PS2-FRI-087

Human microvascular endothelial cell and fibroblast proliferation after cysteamine exposure

M. Besouw* ¹, L. van den Heuvel^1,2, M. Dewerchin³, E. Levtchenko¹

¹University Hospitals Leuven, Belgium, ²Radboud University Nijmegen Medical Centre, The Netherlands, ³Catholic University Leuven, Belgium

Background: Cystinosis is an autosomal recessive disease caused by intralysosomal cystine accumulation, treated with cysteamine. Recently 8 patients were reported with severe muscular-skeletal weakness, bruising-like lesions on elbows and skin striae after administration of high cysteamine doses. Biopsies of elbow lesions showed microvascular proliferation (angioendotheliomatosis) and variable collagen fibre diameter. We studied the mechanisms of these adverse events in human microvascular endothelial cells (HMVEC) and human fibroblasts exposed to cysteamine.

Methods: HMVEC and fibroblasts from healthy controls were incubated with cysteamine (range 0–10 mM) during 6 or 24 hours. Cell viability was measured using WST-1, cell proliferation was measured by BrdU incorporation. WST-1 experiments were repeated in cystinotic fibroblasts from patients with (n = 3) and without (n = 3) cysteamine toxicity. Growth factors (VEGF: vascular endothelial growth factor, PlGF: placental growth factor, b-FGF: basic fibroblast growth factor, PDGF: platelet derived growth factor) were measured in HMVEC supernatant medium after 6 and 24 hours of cysteamine exposure. The paired student t-test was used for statistical analysis.

Results: HMVEC cell viability increased by 135% (p < 0.01) after 24 hours of cysteamine exposure (0–3.0 mM). HMVEC cell proliferation increased by 59% (p < 0.05) and by 31% (p < 0.05) after 6 and 24 hours of cysteamine exposure (0.03–1.0 mM) respectively. No effect was observed in fibroblasts (either control, cystinotic with or without cysteamine toxicity), 10 mM was toxic in all celltypes. Cysteamine 0.03–0.3 mM stimulated VEGF production with 54–95% (p < 0.05) in HMVEC while there was no differences in PlGF, b-FGF and PDGF concentrations.

Conclusion: Cysteamine concentrations described in patients\’ plasma (0.3–1 mM) increase HMVEC proliferation and stimulate VEGF production. We suggest that this mechanism underlies angioendotheliomatosis induced by cysteamine.

PS2-FRI-088

Carnitine suppletion and its effect on carnitine profile in patients with renal Fanconi syndrome due to cystinosis

M. Besouw* ¹, D. Cassiman¹, M. Cornelissen², L. Kluijtmans², E. Levtchenko¹

¹University Hospitals Leuven, Belgium, ²Radboud University Nijmegen Medical Centre, The Netherlands

Background: Cystinosis is an autosomal recessive disorder, marked by intralysosomal cystine accumulation in various tissues. It causes renal Fanconi syndrome, causing carnitine deficiency in plasma and muscles. We aim to determine plasma carnitine profiles in patients with renal Fanconi syndrome due to cystinosis, with and without carnitine suppletion.

Methods: Five genetically-confirmed cystinosis patients with renal Fanconi syndrome, aged 2–18 years, were included. GFR ranged between 21–123 mL/min/1.73 m². L-carnitine was prescribed 50 mg/kg/day since diagnosis of cystinosis, for a median period of 36 (range 18–207) months. Plasma carnitine profiles were measured at baseline, 3 months after stopping L-carnitine and 3 months after reintroducing L-carnitine 50 mg/kg/day.

Results: At baseline, plasma free carnitine was normal in all patients, total carnitine (4/5), acetylcarnitine (2/5) and several small and medium chain acylcarnitines <10 carbons (5/5) were increased. Three months after stopping L-carnitine suppletion carnitine profiles normalized, but plasma free (3/5) and total carnitine (1/5) decreased. Three months after re-introduction of L-carnitine 50 mg/kg/day plasma free carnitine normalized in all patients, but total carnitine (2/5), acetylcarnitine (3/5) and several acylcarnitines <10 carbons (4/5) rose above normal range.

Conclusion: Administration of generally recommended doses L-carnitine (50 mg/kg/day) resulted in carnitine profile changes, characteristic for oversuppletion (increased plasma total carnitine, acetylcarnitine and acylcarnitines <10 carbons). The aims of L-carnitine suppletion are poorly defined, in general, the drug is considered to be rather safe. However, long-term effects of carnitine oversuppletion remain unknown. We suggest that lower carnitine doses might be sufficient to replete carnitine deficiency in cystinosis.

PS2-FRI-090

Loss of nocturnal dipping on 24h ambulatory blood pressure monitoring as an early predictor of diabetic nephropathy

J. Soltysiak* ¹, T. Krynicki¹, A. Musielak¹, P. Fichna², W. Stankieiwcz², B. Skowronska², J. Zachwieja¹

¹Dept. of Pediatric Nephrology; Poznan University of Medical Sciences, Poznan, Poland, ²Dept. of Pediatric Diabetes and Obesity; Poznan University of Medical Sciences, Poznan, Poland

Diabetic kidney disease (DKD) in patients with type 1 diabetes mellitus (T1DM) almost certainly begins soon after disease onset and may lead to microalbuminuria (MA), hypertension (HA) and incipient diabetic nephropathy (DN). To prevent DN, we should detect the earliest manifestations of renal injury. The aim of our study was the assessment of 24 h ambulatory blood pressure monitoring (ABPM) as an early predictor of DN.

Methods: ABPM was performed in 48 children (26 girls and 22 boys) with T1DM. The mean age of patients was 13,74 ± 2,8 years with mean duration of T1DM 5,03 ± 2,9 years. All subjects were normoalbuminuric and presented normal eGFR. We compared the albumin/creatinine ratio (ACR), hemoglobin A1C (HbA1C), triglycerides (TG) levels and body mass index (BMI) in the groups in relation to ABPM values with a special attention to nighttimedipping status.

Results: HA as well as preHA were diagnosed in 11/48 (22,9%). Both HA and preHA had the elevated nighttime MAP. In 32/48 (66,6%) patients we recognized nondipping status. Nondipping compared to dipping patients showed significantly higher levels of HbA1C (9,05 ± 2,47 vs. 7,07 ± 1,07%; p = 0,006), ACR (10,24 ± 5,46 vs. 7,03 ± 2,55 mg/g; p = 0,043), TG = (100,70 ± 77,12 vs. 51,61 ± 18,68 mg/dl; p = 0,069), BMI (21,12 ± 3,37 vs. 19,12 ± 2,49 kg/m²; p = 0,028). Among nondipping subjects the positive correlation have been found between ACR and GFR (r = 0,61; p = 0,001) as well as between ACR and nocturnal diastolic BP (r = 0,51; p = 0,004).

Conclusions: Children with T1DM often suffer from nocturnal HA. Loss of nighttime dipping is an early risk factor for the development of DN and may precede MA.

PS2-FRI-097

Treatment with rituximab in the idiopathic nephrotic syndrome (INS)

A. Madrid* ¹, S. Chocron¹, E. Lara¹, R. Vilalta¹, M. Muñoz¹, C. Herrero¹, J. Nieto¹

¹Hospital Valle Hebron, Pediatric nephrology, Barcelona, Spain

40% of the patients with Nephrotic Syndrome that are steroid-sensitive (SSNS) are relapsing nephrotic syndrome (FRNS), steroid-dependent nephrotic syndrome (SDNS) or steroid-resistant nephrotic syndrome (SRNS).

Oral corticosteroids is the treatment but sometimes for toxicity or resistance, we need immunosuppressant treatment.

Objectives: 1) the efficiency of RTX in controlling the FRNS, SDNS and SRNS; 2) the efficiency of RTX in controlling SRNS and cyclosporine-sensitive (CyAS) and cyclosporine-dependent (CyAD); 3) Duration of remission with RTX and the relation with the immune phenotype; 4) side effects of RTX.

Patients and method: 15 patients (7 boys and 8 girls). Thirteen of them had biopsies. 10 showed Minimal Change Disease (MCD), 3 showed Focal Segmental Glomerulosclerosis (FSGS). 2 doses of RTX were administered at 375 mg/m2/dose at an interval of 1 week. Fourteen patients were in remission and 1 was presenting nephritic proteinuria (patient nº2).The base immunosuppressant to be withdrawn after the RTX.

Results: 10 patients with MCD were steroid-sensitive (SSNS) and they answered to 2 RTX doses. The patients 4 and 5 relapsed 10 months after of RTX and they received 2 more doses and remain in remission until now. The relapse coincided with the reappearance of the lymphocytes B. All 3 FSGS were SRNS; two of them was not responsive to RTX. Of the SRNS CyAS patients, one did not answer to the RTX. Of the 10 patients in remission, 5 of them have recovered the immune phenotype. The average recovery time is 10 months.

Conclusions: 1) all the patients SSNS have responded to RTX; 2) of the 5 patients who have recovered the immune phenotype, only 2 have relapsed; 3) the 2 relapsing were in relation with the recovery of the immune phenotype; 4) the patients with SRNS were resistant to the RTX; 5) no side effects were observed.

PS2-FRI-102

Mycophenolate mofetil as a steroid sparing agent for treatment of severe HSP nephritis

A. Zolotnitskaya* ¹, R. Weiss¹

¹Maria Farreri Children’s Hospital, New York Medical College, New York, USA

Background/objective: Henoch-Schonlein purpura (HSP) is an acute vasculitis that primarily affects children. Severe HSP nephritis constitutes a risk for ESRD, especially in patients presenting with nephrotic syndrome. There are limited data regarding use of mycophenolate mofetil (MMF) for treatment of severe proliferative and crescentic HSP nephrits. We present our experience with MMF as a steroid sparing agent for treatment of severe HSP nephritis in children.Patients and methods. Four patients (mean age 5.8 years, three boys, and one girl) have been followed at our center since 2008. All patients presented with a typical purpuric rash followed by gross hematuria and biochemical nephrotic syndrome. Biopsy findings were consistent with class III (3)and class IV (1) HSP nephritis according to the ISKDC. Treatment protocol included IV methylprednisolone 10 mg/kg for three consecutive days followed by oral daily prednisolone, 2 mg/kg/day, for at least 6 weeks followed by 6 weeks of alternate day prednisolone, 2 mg/kg. Two patients were started on MMF as a steroid sparing agent at a dose of 600 mg/m2 BID after 6-weeks of daily steroids failed to decrease proteinuria. In two patients MMF and oral prednisolone were started simultaneously. Trough mycophenolic acid levels were maintained within therapeutic range. Results. None of the four patients suffered GFR impairment. Mean Up/c at the start of MMF was 5.8. Four weeks after the start of MMF mean U p/c decreased to 1.07. After eight weeks of MMF therapy mean U p/c declined to 0.48. Mean duration of MMF therapy was 7 months. MMF was successfully withdrawn in all patients with no rebound disease activity observed.

Conclusion: Our results indicate that MMF may be an attractive steroid sparing or adjunctive agent for treatment of severe HSP nephritis.

PS2-FRI-103

Rituximab as a non-standard immunosuppressive therapy in children with nephrotic syndrome—a single pediatric nephrology center experience

A. Musielak* ¹, M. Silska¹, K. Lipkowska¹, A. Warzywoda¹, J. Sołtysiak¹, A.Blumczynski¹, D. Ostalska-Nowicka¹, J. Zachwieja¹

¹Department of Pediatric Cardiology and Nephrology, Poznan University of Medical Sciences, Poland

Objectives and study: Anti-CD20 monoclonal antibodies are promising for the treatment in children with nephrotic syndrome who were not eligible for routine treatment. The aim of our study was to analyze the efficacy and safety of Rituximab, chimeric monoclonal antibody against lymphocytes CD20, as a non-standard immunosuppressive therapy.

Methods: In study 15 children (10 girls, 5 boys) with non-responding to standard immunosuppressive therapy proteinuric glomerulopathies have participated. Inclusion indications were: drug-resistant nephrotic syndrome (n = 13), steroid-dependent nephrotic syndrome (n = 2). All have undergone a renal biopsy. Patients were treated with rituximab 375 mg/m2 intravenously every 6 months for 6–15 months. Eleven patients were receiving only Rituximab. Evaluation of proteinuria and plasma percentage of CD19 lymphocytes was done at intervals of one, three and six months after which five patients received a single booster dose.

Results: The complete remission defined as proteinuria less than 150 mg/24 h, was observed in 11 of the 15 children. The partial remission (proteinuria less than 50 mg/kg/24 h and more than 150 mg/24 h, and normal serum albumin concentration) was observed in four patients (all of them was simultaneusly treated with cyclosporine A). GFR less than 60 ml/min/1.74 m2 was present in one patient. There were no statistical correlations between age, sex and number of CD 19. No serious infections of the respiratory system or biochemical side effects (monitored by peripheral leucocytosis, plasma cystatin C, creatinine and concentration of IgG) were observed.

Conclusions: Rituximab therapy should be taken into consideration in non-responding to standard therapy children with nephrotic syndrome. Benefits of Rituximab treatment in these group of patients are higher than possible side-effects.

PS2-FRI-106

The serum concentration of serum amyloid a protein (SAA) in patients with juvenile rheumatoid arthritis (JRA) depending on the proteinuria

A. Stepanova* ¹

¹Saint-Petersburg State Pediatric Medical Academy, Saint-Petersburg, Russian Federation

Background: The aim of the investigation is to estimate SAA concentration in sera of children with JRA depending on proteinuria degree, to compare SAA concentration with clinical presentations of kidney involvement.

Methods: 39 children with JRA (aged 3–17 years) were examined, among them—14 boys, 25 girls. In sera of patients SAA concentration was measured by an enzyme linked immunosorbent assay. Normal serum SAA concentration is under 10–15 mg/l.

Results: 22 patients (56,4%) had articular form of JRA, 17 (43,6%) had systemic JRA. The duration from the onset of JRA by the time of catamnesis was from 3 months till 16 years (5,2 ± 0,7 years). The therapy of JRA was conducted by nonsteroidal antiinflammatory drugs (NSAIDs), glucocorticoids (including methylprednisolone pulse-therapy), cytostatic drugs. 39 patients with JRA had normal GFR. 12 of 39 patients (30,8%) had proteinuria less than 1 g/m2/24 h, proteinuria wasn’t identified in 27 patients (69,2%).

Increased serum SAA concentration (333,4 ± 40,0 mg/l) was revealed in 37 children (94,9%). Of 27 patients with JRA without proteinuria 2 (7,4%) had normal serum SAA concentration, in 25 patients (92,6%) increased SAA concentration (247,6 ± 45,6 mg/l) was observed. In 12 patients with proteinuria increased serum SAA concentration (512,1 ± 48,5 mg/l) was diagnosed. SAA concentration in 12 patients with proteinuria was authentically higher than SAA in sera of 27 patients without proteinuria (p < 0,001).

Conclusions: The results revealed that serum SAA concentration in patients with JRA and proteinuria was higher than in patients without proteinuria.

Renal biopsy should be carried out to 12 patients with JRA, proteinuria and increased serum SAA concentration to differentiate between secondary renal AA amyloidosis in proteinuric stages and membranous nephropathy associated with NSAIDs.

PS2-FRI-109

Bright kidneys on fetal ultrasonography—a rare differential diagnosis

B. Bucher* ¹, R. Müller², S. Fluri², B. Tutschek³, S. Tschumi¹, J. M. Nuoffer⁴, G. D. Simonetti¹

¹Division of Pediatric Nephrology, Children’s Hospital, University of Bern, Bern, Switzerland, ²Department of Neonatology, Children’s Hospital, University of Bern, Bern, Switzerland, ³Obstetrics and Gynaecology, University Hospital, Bern, Switzerland, ⁴Division of Pediatric Metabolic Disorders, University Children’s Hospital, University of Bern, Switzerland

Introduction: Some diseases can prenatally present with enlarged hyperechogenic kidneys^, autosomal recessive polycystic kidney disease being the most frequent. We describe the case of a newborn girl with a rare disease, which infrequently may prenatally present with hyperechogenic and enlarged kidneys.

Case: At 22 weeks of gestation, fetal ultrasound of a healthy secondipara with unremarkable personal and familial history revealed enlarged hyperechogenic kidneys without any other abnormalities. At that time a tentative diagnosis of autosomal recessive polycystic kidney disease was made. At 29 weeks of gestation, oligohydramnion, mild cardiomegaly and cystic enlargement of the septum pellucidum were additionally found. Amniocentesis disclosed a normal caryotype (46 XX) and fetal MRI confirmed the findings on ultrasound.

Because of increasing oligohydramnion and asymmetric growth retardation, elective caesarean section was performed at 36 1/7 weeks. The hypotrophic girl had a good initial adaptation, diuresis and creatinine were within normal range and abdominal ultrasonography showed enlarged, polycystic kidneys. The girl presented a relative macrocephaly, a big and prolapsing fontanelle, flat ears and a generalized muscular hypotonia. Cerebral ultrasound demonstrated bilateral calcification of basal ganglia, an echocardiography revealed ventricular hypertrophy. On the second day of life the girl developed tachypnea, lactic acidosis with hyperammonemia and an odour of sweaty feet. Diagnosis of glutaric aciduria type II was confirmed by organic acids and acylcarntine profile. Therapy with benzoate, carnitine and riboflavin did not improve the condition and in view of the infaust prognosis of the neonatal form of the disease, active treatment was terminated. The girl died on third day of life.

Conclusion: Glutaric aciduria type II should always be considered when enlarged kidneys are observed on fetal ultrasonography, especially if there are other organ abnormalities, such as cardial or cerebral malformations. Prenatal diagnostic possibilities to confirm the diagnosis are available.

PS2-FRI-116

Response to growth hormone in children with chronic kidney desease (CKD) in conservative treatment. a single center experience

C. Fernandez Camblor* ¹, M. Carrasco Hidalgo², M. Navarro Torres¹, L. Espinosa Roman¹, M. Melgosa Hijosa¹, A. Peña Carrion¹, C. Garcia Meseguer¹, A. Alonso Melgar¹

¹Hospital Infantil, “La Paz”, Madrid, Spain, ²Hospital “Infanta Cristina” de Badajoz, Madrid, Spain

Objective: Evaluate growth hormone (rhGH) treatment in conservatively treated CKD children.

Materials & methods: A retrospective study of 48 patients (29♂ 19♀) treated with rhGH. Data were recorded every six months beginning from one year prior to initiating treatment to three years later. The underlying diseases were: structural: 50%; hereditary 35.4% and others: 14.6%. Age at beginning rhGH was 9 + 4 years (2.4–16.8 yrs). 68% were prepubertal. GFR (Schwartz formula) on beginning rh GH was 45 ± 28 ml/min/1.73 m² (20% stage 2, 45% stage 3, 35% stages 4 and 5 of CKD).

Results: Data of SD height: −1 year: −1.9 + 1.1; −6 month: :−1.9 + 0.1; initiating rhGH: −2 + 0.9 6 month: : −1.6 + 1; 1 year: −1.5+ 0.9; 18 months: −1.4+ 1; 2 years: −1.3 + 1; 2.5 years: −1.2 + 1.2 , 3 years: −1.4 + 1.1. Significant increase(p < 0.005) in SD height in the first 2.5 years, first six months’ maximum growth; 1st year growth rate: 8.9 + 2.5 cm; No changes in SD weight, SD IMC, GFR, IGF-1; calcium; phosphate; parathormone (PTH), haemoglobin, bicarbonate, bicarbonate intake or eritropoyetin dose. No patient has had thyroid dysfunction, significant increase in Hb A1C, or intracraneal hypertension. Gender did not affect response. Final adult height for girls (7): 154.5 + 5.9 cm (0.94 + 1.2 SD height), boys (10): 167.8 + 8 cm (0.94 + 1.2 SD height). Compared to their pre-treatment height, the children’s height had improved by a 1.02 + 0.8 SD. There is a significant inverse relation between the response to rhGH and the age of initiating treatment. The response to rhGH was independent of the degree of CKD, underlying disease, nutritional status, gender, haemoglobin, PTH or IGF-1.

Conclusion: rhGH is safe, and improves growth, specially in the first years of treatment, most notably in younger children; it does not affect GFR and helps children reach normal adult height.

PS2-FRI-118

Epidemiology of glomerular diseases documented by renal biopsy in children

D. Kuzmanovska* ¹, E. Sahpazova¹, S. Timovska¹, G. Petrusevska²

¹Pediatric Clinic, Medical Faculty, St. Cyril & Methodius University, Skopje, Macedonia, ²Institut for pathology, Medical Faculty, St. Cyril & Methodius University, Skopje, Macedonia

Objectives: This study aimed to determine glomerular disease frequencies in children in R.Macedonia and it represents the basis for future studies.

Methods: All native renal biopsies (January 1996 to December 2008) were reviewed; only glomerular diseases were analyzed. The diagnosis of each case was based on histological, immunopathological and clinical features. As University Paediatric Clinic in Skopje is the only paediatric nephrology centre in the country, the results of this study relate to the whole country.

Results: A total of 82 patients <15 years (mean age 8.59 ± 3.9%) were included in the study. Primary glomerular diseases were diagnosed in 65 biopsies (79%) and secondary in 17 (21%).The most common primary diseases were minimal change disease (35%) , mesangiproliferative glomerulonephritis (17%), immunoglobulin A nephropathy (14%), focal and segmental glomerulosclerosis (12%), membranous glomerulonephritis (8%), crescentic glomerulonephritis (3%). Postinfectious glomerulonephritis (GN) represented 8% of the diagnoses if included as primary GN. In the group of secondary glomerulonephritis, Henoch Shonlein nephritis corresponded to 59% of the entire series and lupus nephritis to 29%. Alport syndrome was found in 12%.

Conclusions: The distribution of glomerular diseases in the paediatric age group at R.Macedonia is similar to that described in other countries with some differences. This study illustrates the importance of having a regional register for renal diseases in children.

KEY WORDS: Epidemiology. Glomerulonephritis. Children Database. Renal biopsy.

PS2-FRI-122

A child with specific ADAMTS-13 gene defect

D. Milošević* ¹, D. Batinić¹, K. Vrljičak¹, Lj. Nižić¹, D. Turudić¹, J. A. Kremer Hovinga²

¹Department of nephrology, University of Zagreb Medical School, University Children’s Hospital Zagreb, Zagreb, Croatia, ²Hemostasis Research Laboratory, Inselspital, Bern University Hospital & University of Bern, Bern, Switzerland

Objectives and study: A child with confirmed ADAMTS 13 gene defect was treated with plasma therapy substitution.

Methods: VWF-cleaving protease activity evaluation, gene determination, clinical and laboratory follow-up.

Results: A 4 year old child was admitted in Clinical hospital after recidivant episodes of haemolytic anaemia registrated in early childhood. Haemolytic anaemia (Hb 90 g/L, Htc 0.27 L/L), thrombocytopenia (31 × 10 9 /L), macrohematuria, proteinuria (089 g/24) with mild renal insufficiency (270 μmol/L) were assessed. After fresh frozen plasma, plasmapheresis and thrombocyte infusions administration, kidney biopsy revealed histological image consistent with hemolytic-uraemic syndroma in 25% of all glomeruls. After repeated episode of macrohaematuria, haemolytic anaemia and thrombocytopenia vWF cleaving protese activity was determined (<3%). Parental and sister cleaving protease activity was normal. ADAMTS-13 gene determination revealed mutations: Exon 9: Cys 347 Ser. The affected nucleotide is 1039 T → A. A mutation was inherited from his father. His sister is heterozygous for this mutation. Exon 29: 4143 ins A (an insertion of a nucleotide A at position 4144). This results in a frameshift and a premature stop codon at amino acid 1386 (normal full-length protein has 1427 amino acids).

Periodical fresh frozen plasma (10 ml/kg) every 3–4 weeks were adminstered, Hepatitis B vaccination was managed and control blood count, immunology and renal function tests periodically performed. After recidivant respiratory infections, tonsilloadenoidectomy was performed.

Conclusions: A child with ADAMTS-13 TTP mutation is treated with repeated plasma infusions. During substitution, urticarial rush is occasionally noticed and dealed with corticosteroid and/or histamine antagonists. No further TTP episodes, hematuria or proteinuria were noticed. Renal function remains stabile and within normal limts.

PS2-FRI-125

mTOR signaling is differentially affected in human renal cells with PKD1 or PKD2 mutations

D. Mekahli* ^1,2, E. Sammels¹, J. P. Decuypere¹, M. P. Audrezet³, G. Dechênes⁴, A. Ong⁵, L. van den Heuvel⁶, L. Missiaen¹, H. De Smedt¹, E. Levtchenko^2,6

¹Laboratory of Molecular and Cellular Signalling, Department of Molecular Cell Biology, K.U.Leuven, Campus Gasthuisberg O&N1, Leuven, Belgium, ²Department of Pediatric Nephrology, University Hospital Gasthuisberg, Leuven, Belgium, ³Laboratoire de Génétique Moléculaire, CHU—INSERM U613, Brest, France, ⁴Department of Pediatric Nephrology, Hôpital Robert-Debré, Paris, France, ⁵Academic Unit of Nephrology University of Sheffield, Sheffield, UK, ⁶Laboratory of Pediatrics, K.U.Leuven, Campus Gasthuisberg O&N1, Leuven, Belgium

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic disorder leading to end stage renal disease (ESRD). It is caused by loss-of-function mutations in either PKD1 (85%) or PKD2 (15%) genes which encode polycystin-1 (PC1) and −2 (PC2) respectively. Patients with PKD2 mutation have a milder phenotype and reach ESRD ∼20 years later than those with PKD1 mutation.

Increased activity of mammalian target of rapamycin (mTOR) pathway has been shown in PKD1 mutants and is implicated in accelerated cell proliferation. Furthermore, it has been demonstrated that rapamycin, an inhibitor of mTOR, is highly effective in reducing renal cystogenesis in rodent models with PKD1 mutations. However, mTOR activity in PC2 mutants has not been studied thus far.

Methods: We developed conditionally immortalized human proximal tubule epithelial cell lines (ciPTEC) from patients with known PKD1 and PKD2 mutations and from healthy controls. Also, we generated stable PC1 and PC2 knockdown (KD) cell lines using lentiviral vectors expressing miRNA-based shRNA. In these models we measured the mTOR activity (phosphorylated ribosomal protein S6) via Western blotting.

Results: We confirmed in the PC1 KD cell line and in ciPTEC with PKD1 mutations an upregulation of mTOR activity compared with controls (160% vs 100% respectively; p = 0.005). In contrast, in the PC2 KD cells and ciPTEC from patients with PKD2 mutations mTOR activity was in the range of control cells (80% vs 100% respectively; p = 0.350).

Conclusion: This is the first report that highlights an important difference in the underlying molecular mechanism between PKD1 and PKD2 mutations. Using human renal cell models of ADPKD, we demonstrate that mTOR activity seemed not to be affected by the downregulation of PC2. This might explain the milder renal phenotype in these patients. Our data can have important therapeutic implications for selecting patients for treatment with mTOR inhibitors.

PS2-FRI-126

Knockdown of polycystin-1 and −2 reduces the Ca2+ leak from the endoplasmic reticulum, increases the store Ca2+ content en subsequently decreases store-operated Ca2+ entry

D. Mekahli* ^1,2, J. Schoeber³, R. Ponsaerts¹, J. B. Parys¹, M. P. Audrezet⁴, G. Dechênes⁵, L. van den Heuvel³, E. Levtchenko^2,3, L. Missiaen¹, H. De Smedt¹

¹Laboratory of Molecular and Cellular Signalling, Department of Molecular Cell Biology, K.U.Leuven, Campus Gasthuisberg O&N1, Leuven, Belgium, ²Department of Pediatric Nephrology, University Hospital Gasthuisberg, Leuven, Belgium, ³Laboratory of Pediatrics, K.U.Leuven, Campus Gasthuisberg O&N1, Leuven, Belgium, ⁴Laboratoire de Génétique Moléculaire, CHU—INSERM U613, Brest, France, ⁵Department of Pediatric Nephrology, Hôpital Robert-Debré, Paris, France

Background: Mutations in the genes encoding the polycystin-1 (PC1) and −2 (PC2) proteins lead to autosomal dominant polycystic kidney disease (ADPKD), the most common inherited nephropathy leading to renal failure. Several mechanisms by which PC1 and −2 may affect Ca2+ signaling have been proposed, however a general picture is lacking. There is also no clue about the interdependence of both PC’s in these processes. We developed human cell lines with either PKD1 or PKD2 mutations in order to measure potential changes in their intracellular Ca2+ signaling.

Methods: Conditionally immortalized human proximal tubule epithelial cell lines (ciPTEC) were developed from urine of patients with ADPKD and from healthy controls. Additionally, we generated stable PC1 and PC2 knockdown (KD) ciPTEC cell lines using lentiviral vectors expressing miRNA-based shRNA. We investigated changes in intracellular Ca2+ signaling using Fura-2 as a fluorescent Ca2+ indicator in a microtiter plate assay (FlexStation).

Results: We demonstrate that ciPTEC from ADPKD patients had altered Ca2+ signaling as compared to control cells. PKD2 mutants demonstrated a less sensitive agonist (ATP)-induced Ca2+ release. The dose–response curve of Ca2+ release as a function of the [ATP] was thereby shifted to higher doses, while PKD1 mutants were not different from controls. Moreover, we found that the knockdown of both PC1 and −2 reduced the Ca2+ leak from the endoplasmic reticulum (ER), increased the store Ca2+ content en subsequently decreased store-operated Ca2+ entry.

Conclusion: ciPTEC lines with a mutation in PKD2 are less sensitive to the addition of extracellular ATP. Moreover, knockdown of PC1 and −2 decreased the Ca2 + −leak from the ER, which probably occurs via PC2 or via the IP3R. Blocking this Ca2 + −leak pathway in ADPKD may be responsible for a decrease in the cytosolic [Ca2+].

PS2-FRI-133

Protease inhibitors provided with proteasome inhibitor activity have a direct effect on cultured human podocytes

E. Loiacono* ¹, V. Fonsato², R. Camilla¹, L. Peruzzi¹, L. Morando¹, R. Gallo¹, L. Vergano¹, F. Campolo¹, V. Daprà¹, R. Coppo¹

¹Nephrology, Dialysis and Transplantation—Regina Margherita Hospital, Turin, Italy, ²Internal Medicine, University of Turin, Turin, Italy

Objectives and study: Bacterial lypopolysaccharide (LPS) signaling through toll-like receptor (TLR)-4 reorganizes the actin cytoskeleton of podocytes, causing proteinuria in animal models. TLR ligation induces nuclear translocation of nuclear factor kB (NF-kB) subunits (p50 and p6), after proteasome processing of the inhibitor protein IkB. The process is blunted by antiretroviral protease inhibitors which we demonstrated to induce proteasome inhibition (AIDS 2002; 16:693–700), and be beneficial in cases of steroid-dependent nephrotic syndrome. In these patients NF-kB is enhanced in peripheral mononuclear cells and downregulated by protease inhibitors. Aim of this study was to investigate the effect of the anti retroviral protease inhibitor ritonavir in experimental conditions -challenge with LPS or TNFα- known to induce podocytary surface proteins and/or cytoskeletal actin reorganization.

Methods: Primary culture of human glomerular epithelial cells were established and characterized as described (JASN 2005; 16:1936–47) and incubated with TNFα 20 ng/ml or LPS 10 μg/ml for 1 hour in ritonavir graded concentrations (up to 40 μMol). Nuclear extracts were tested for NF-kB p50 and p65, cytoplasmic estracts for cytoskeletal actin by western blot.

Results: In cultured podocytes TNFα and LPS triggered the nuclear translocation of NF-kB in comparison to basal conditions (TNFα: p50 = 44 vs 27 U; p65 = 20 vs 11 U; LPS: p50 = 48 vs 17 U; p65 = 26 vs 9 U) and reduction in cytoskeleton actin. On both effects ritonavir induced dose-dependent blunting results (TNFα + ritonavir 10 μMol: p50 = 32, p65 = 11 U; TNFα + ritonavir 20 μMol: p50 = 20, p65 = 8 U; LPS + ritonavir 10 μMol: p50 = 37, p65 = 12 AU; LPS + ritonavir 20 μMol: p50 = 28, p65 = 10 U).

Conclusions: The protease inhibitor ritonavir inhibits in cultured podocytes the activation of NF-kB triggered by LPS and TNFα, suggesting that podocytes may be a direct target of these drugs, till now considered a modulator of some soluble permeability factors regulated by circulating cells.

PS2-FRI-140

CKR-1 may play a role in inflammation in experimental mesangioproliferative glomerulonephritiS

F. Ozaltin* ¹, N. Besbas¹, A. B. Iskit², O. Cil¹, Z. Akcoren¹, G. Kale¹, A. Bakkaloglu¹

¹Hacettepe University Faculty of Medicine, Dept. of Pediatrics, Ankara, Turkey, ²Hacettepe University Faculty of Medicine, Dept. of Pharmacology, Ankara, Turkey

CKR-1 (CXCR-1), receptor of interleukine 8, plays a major role in proliferating glomerular diseases. We investigated renal expression of CKR-1 and effect of single intravenous dose cyclosporine A (CsA) treatment on its expression in experimental mesangioproliferative glomerulonephritis induced by anti-thymocyte serum (ATS). Animals were divided into 3 groups. Group 1 rats (n = 24) received ATS only. Group 2 rats (n = 24) received both ATS and CsA concomitantly. Control rats (n = 24) received non-immune serum. Kidneys from 6 rats in each group were removed at 6th hour, 3rd, 5th and 7th days. Expression of CKR-1 and other histological parameters were evaluated semiquantitatively in glomeruli and tubulointerstitium of kidneys by immunohistochemistry. 24 hour urine samples were obtained before nephrectomies and urinary protein/creatinine ratios were calculated. ATS induced significant proteinuria compared to controls (p < 0.001) and CsA prevented development of proteinuria. Glomerular inflammatory cells were significantly increased in ATS group compared to both controls and CsA treated rats (p < 0.001). Mesangial proliferation induced by ATS became obvious in the first day after injection and reached maximum around 5th and 7th days (p < 0.001). CsA was not effective in terms of preventing mesangial proliferation. ATS injection caused marked renal interstitial inflammation, which started in the first day following injection period and increased gradually in the course of time. Interstitial inflammation, which was precluded by CsA in the 6th hour appeared on the following days. CKR-1 was not expressed in control group, however ATS injection resulted in expression of CKR-1 in both glomeruli and tubulointerstitium in early period and persisted during the time course. While CsA treatment prevented CKR-1 expression in both glomeruli and tubulointerstitium in the first 6 hours after ATS injection, no significant effect was observed in the following days. In conclusion, our findings suggest that CKR-1 may contribute inflammation in both glomeruli and tubulointerstitium in experimental mesangioproliferative glomerulonephritis.

PS2-FRI-145

Mycophenolate mofetil therapy in children with steroid-dependent and—resistant nephrotic syndrome

F. Baştuğ* ¹, R. Düşünsel¹, Z. Gündüz¹, İ. Dursun¹, H. Poyrazoğlu¹, S. Tülpar¹, S. Yel¹

¹Erciyes University Medical Faculty Department of Pediatric Nephrology, Kayseri, Turkey

Backgraund: Steroid sparing agents have been used in reducing the risk of relapse in children with in steroid-dependent (SDNS) and steroid resistance nephritic syndrome (SRNS). The aim of this study was to determine the effect of the mycofenolate mofetil treatment in patients with SDNS and SRNS experience frequent relapses despite long-term treatment with steroids, cyclosporine A (Cs-A), azathioprine, levamisole, or/and cyclophosphamide.

Material-method: We reviewed the charts of 4 patients with SDNS and 5 patients with SRNS. The patients with a mean age at diagnosis of 4.5 years (range 2.5 to 7 years) who had previously undergone long-term therapy with prednisolone (n = 9), Cs-A (n = 9), pulse methylprednisolone (n = 7), azathioprine (n = 5) levamisole (n = 3), and cyclophosphamide (n = 5), but had continued to show steroid dependence over many years, were studied. Renal biopsy showed minimal change disease, focal-segmental glomerulosclerosis and IgM nephropathy in 3, 3 and 1 patients, respectively. All patients were treated with MMF, at 1,200 mg/m 2 per day in 2 divided doses, in an attempt to allow weaning of Cs-A and/or steroid therapy, and reduce the frequency of relapses.

Results: Mean relapse rates decreased from 9.6 (5 to 16) to 2 episodes/year (1.5 to 2.8) during MMF treatment in 4 of 9 patients. Three of these 4 patients had SDNS, 1 had SRNS. Treatment with MMF resulted in steroid sparing, with a reduction in mean prednisolone dose from 0.7 to 0.3 mg/kg/d in these patients. Other patients didn’t have a significant decrease in relapse rates during MMF therapy. No significant gastrointestinal or hematologic side effects of MMF treatment were noted.

Conclusion: Long-term therapy with MMF results in significant steroid sparing and reduction in relapse rates in patients with SDNS but not with SRNS. Therapy with MMF and tapering doses of prednisolone appears to be a promising intervention in children with SDNS.

PS2-FRI-148

Hemolytic-uremic syndrome in children in Norway, 1999–2008

G. R. Jenssen* ^1,2, H. J. Bangstad³, A. K. Bjerre³, L. Vold¹, K. Nygård¹, E. Hovland^1,2

¹Department of Infectious Disease Epidemiology, Division of Infectious Disease Control, The Norwegian Institute of Public Health, Oslo, Norway, ²The Medical Student Research Program, Faculty of Medicine, University of Oslo, Oslo, Norway, ³Department of Pediatrics, Oslo University Hospital, Oslo, Norway

Objectives and study: Hemolytic-uremic syndrome (HUS) is characterized by the triad of acute renal failure (ARF), microangiopathic anemia and thrombocytopenia. Mainly affecting children, HUS is associated with potentially life-threatening complications. It is divided into diarrhea-associated (D + HUS) and non-diarrhea-associated. Enterohemorrhagic Escherichia coli (EHEC) infection is the most common cause. Our aim was to identify age-specific rate and distribution of etiology of HUS among children (o-16 years) in Norway, 1999–2008.

Methods: Retrospective, descriptive study, based on data from patient journals from pediatric departments in Norwegian hospitals. Search criteria were ICD-10 codes D59.3 (HUS) and N17 (ARF). Inclusion criteria was the characteristic clinical triad. In complicated cases, reported schiztocytes in blood smear and hemolysis, with elevated LD, were diagnostic.

Results: A total of 49 HUS cases were identified, 39 (79,6%) were D + HUS. Estimated overall yearly incidence rate is 0,51 per 100000 inhabitants/year. EHEC infection was confirmed in 23 (46,9%) cases (11 (47,8%) O103, 5 (21,7%) O157), with an incidence rate of EHEC-related HUS of 0,24 per 100000 inhabitants/year. 18 (36,7%) had unknown, 3 (6,1%) genetic and 2 (4,1%) pneumococcal etiology. Highest proportion of cases, 18 (36,7%) and 10 (20,4%), was in 2006 and 2005, respectively, otherwise an average occurrence of 3/year. 38 (77,6%) cases were children aged 0–4 years, 16 (32,7%) 1-year-olds.

Conclusions: The incidence of HUS in Norway is low, with little yearly variation, excluding 2005 and 2006. Highest proportion of HUS cases is in children aged 0–4 years. Highest occurrence (2006) correlate with a known outbreak of O103, being the most common etiology, followed by O157. There are few diagnosed pneumococcal and genetic HUS cases in the period.

PS2-FRI-152

Adenine phosphoribosyltransferase (APRT) deficiency: an underdiagnosed cause of lithiasis and renal failure

G. Marra* ¹, P. G. Vercelloni¹, G. Manzoni¹, G. Garigali¹, G. B. Fogazzi¹, I. Ceballos-Picot², M. A. Pavesi¹, L. Mockel²

¹Fondazione IRCCS Ca\’Granda Ospedale Maggiore Policlinico, Milan, Italy, ²Necker-Enfants Malades Hospital, Assistance-Publique-Hôpitaux de Paris, France

Introduction: APRT gene mutation is an uncommon and underdiagnosed cause of renal stones, due to a defect of uric acid catabolism that leads to accumulation of 2,8 dihydroxiadenine (2,8 DHA). If untreated it can cause severe long-term consequences in adult age as CKD and it can even relapse on the transplanted kidney. We report here a case of 2,8 DHA nephrolithiasis diagnosed during childhood.

Case report: A.P. was born at 29th week of gestational age in a twin pregnancy. During neonatal period US exams showed micropapillary calcifications evolved into some bilateral apico-papillary stones (diameter <6 mm) starting from 16 months of age.

At 18 months of age he suffered from renal colic due to a stone obstructing the internal urethral meatus. A cistoscopic lythotripsy permitted to extract it. Its spectrophotometric analysis revealed a curve similar to that of 2,8 DHA, so an APRT deficit was suspected and allopurinol was started. Exams showed no other metabolic lithogenic alterations. The analysis of the gene confirmed the disease with two gene mutations in heterozygosis of the exon 2: one was present even in his father’s DNA, the other one was a “de novo” mutation. After therapy was started, micropapillary deposits disappeared and no new stones formed .

Discussion: Lithiasis during the pediatric age is a relatively rare condition, but it can be a major indicator of a congenital or metabolic disorder that if diagnosed could be treated sometimes with good clinical results. For this reason, a scrupulous metabolic evaluation in every child with urinary stones is mandatory. APRT deficiency diagnosis is possible with urinary sediment examination, a first diagnostic step in every child with lithiasis, but final diagnosis is possible only with an high index of suspicion and need a multi-disciplinary approach.

PS2-FRI-153

A genotype-phenotype correlation study: determining PKHD1 gene by DNA sequence analysis in autosomal recessive polycystic kidney disease

G. Özçelik* ¹, Ü. Çetinçelik¹, Ö. Bülbül², N. Akıncı¹

¹Department of Pediatric Nephrology, Şişli Etfal Tranning ve Research Hospital, Istanbul, Turkey, ²Department of Medical Biology and Genetic,Enstitute of Medical Sciences, 9 Eylül University, Istanbul, Turkey

Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a single gene disorder with kidney and liver involvement. To be able to determine the disease’s prognosis and the treatment, the mutation analysis for the gene PKHD1 seems very important. Aim of the study is to screen the mutations of the gene PKDH1 in Turkish patients with ARPKD in 10 different exons.

This study carried out in 6 unrelated patients by taking DNA was isolated from the peripheral blood. By this DNA’s the 14, 15, 16, 32, 33, 34, 53, 54, 58 and 60 numbered of exons of PKHD1 gene were amplified by PCR (Polymerase Chain Reaction) DNA sequencing analysis was performed each PCR product of exons, the data was evaluated in the necessary condition two sides PCR and repeat was performed. The mutations and SNP’s were determined by evaluating the sequencing data. The PCR-sequencing analyses results in the PKHD1 gene, at 6 patients were founded two new mutations and in another two patients with defined missense mutation, one intronic changes were obtained. Two patients with a new identified mutation were severely affected. Chronic renal failure and serious hypertension were present at younger age. However, the clinical symptoms of the other patients were not severe. The patients with defined homozigot mutation had hepatic involvement. In conclusion, various type of the mutations at Turkish patients with PKDH1 gene should be kept in mind at screening of these patients. New mutations and new changes have been pointed out, permitting us to contribute to the literature as long as we evaluated the data according to genotype-fenotype correlations.

PS2-FRI-154

Long-term treatment with cinacalcet for secondary hyperparathyreoidism in 5 children and adolescents with chronic kidney disease

H. Staude* ¹, E. Drueckler¹, U. Jacoby¹, D. Haffner¹, M. Wigger¹

¹Department of Pediatrics, University Hospital of Rostock, Rostock, Germany

Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a single gene disorder with kidney and Introduction: secondary hyperparathyreoidsm is an important factor in the pathogenesis of renal osteodystrophy and is associated with cardiovascular morbidity and mortality. In adult CKD patients cinacalcet is an efficacious therapeutic option, particulary in patients with elevated calcium-phosphorus product. Treatment with cinacalcet has been shown to reduce PTH secretion in a dose dependent manner. The long-term effects of cinacalcet in the pediatric CKD patients is not known. Patients and methods: five patients (median age: 10.4 years, range 1.4-21) suffering from CKD and uncontrolled sHPT were treated with cinacalcet for a mean period of 2.7 years (range 1.0–5.3). The initial dosages of 0.24–0.33 mg/kg/day were titrated as high as 1.29 mg/kg/day according to PTH concentrations and adverse effects. Data were collected retrospectively.

Results: all patients showed a marked and sustained decrease in serum iPTH with a reduction of 76% in comparison to pretreatment serum levels (689 ± 240 vs. 158 ± 56 pg/ml, p < 0.05). Furthermore there was a slight reduction of serum calcium (2.48 ± 0.22 vs. 2.42 ± 0.13 mmol/l) and serum Ca x P product (4.90 ± 2.04 vs. 3.43 ± 0.36 mmol2/l2). The administration of cinacalcet had no significant impact on treatment with phosphate binders, but medication with calcitriol was possible to intensify. One patient exhibted asymptomatic hypocalcemia and dosage of cinacalcet had to be reduced to 0.13 mg/kg/day.

Discussion: cinacalcet seems to be an effective treatment modality in children with chronic kidney disease. However, long-term studies are necessary to proof efficiency and safty.

PS2-FRI-158

Treatment of lupus nephritis with rituximab: a case report

H. Pinto* ¹, I. Brito², C. Afonso¹

¹Pediatric nephrology unit, Pediatrics Service, Hospital S. João, Oporto-Portugal, ²Pediatric rheumathology unit, Hospital de S. João, Oporto-Portugal

Therapy of systemic lupus erythematosus (SLE) is currently a challenging issue due to its multiple organ involvement, progressive evolution and intermittent flare deterioration. Conventional immunosuppressive regimens sometimes fail to treat severe manifestations.

We report a case of a 19-year-old girl with juvenile SLE. Her first manifestation was nine years earlier with auto-immune anaemia and thrombocytopenia, treated with prednisolone and immunoglobulin. Eight months later, immunological analysis revealed for the first time low C4 and positive dsDNA antibodies. At this time she maintained thrombocytopenia and it was started azathioprine. Evolution was initially favourable with normalization of platelet count. Two years after presentation she presented malar rash and four years later renal involvement with biopsy proven class IV lupic nephritis that motivated six mensal cycles of cyclophosphamide and maintainance therapy with mycophenolate mofetil. She was asymptomatic for one year and thereafter evidenced nephrotic syndrome associated with decreased glomerular filtration rate (73,3 ml/min/1.73 m²). Findings at second renal biopsy were similar to the first one. She was unresponsive to three cycles of methilprednisolone and oral prednisolone. Due to the severity of the case, therapy with rituximab (antiCD20) was attempted (375 mg/m2 for three consecutive weeks), with no significant side effects and evidencing rapid decrease of proteinuria and normalization of renal function. At present, 20 months later, the patient is still at clinical remission with only residual proteinuria. Rituximab seems to be a promising therapy in severe and conventional-immunosuppressor refractory SLE. Prospective studies must be undertaken in order to evaluate its effectiveness and safety in the paediatric population.

PS2-FRI-165

Evaluation of children with IgA nephropathy according to Oxford classification

Dursun* ¹, R. Dusunsel¹, Z. Gunduz¹, M. H. Poyrazoğlu¹, S. Yel¹, S. Tülpar¹, T. Patıroğlu², F. Bastug¹, H. Akgun²

¹Erciyes University Faculty of Medicine, Department of Pediatric Nephrology, Kayseri, Turkey, ²Erciyes University Faculty of Medicine, Department of Pathology, Kayseri, Turkey

Background: Primary IgA nephropathy (IgAN) is the most common glomerular disease in children who undergo kidney biopsy because of hematuria. It was initially considered a benign condition, but extended follow-up of patients indicated that 9% of the patients had developed chronic renal failure by 15 years. To expect the outcome in patients with IgAN, new classifications were put into practiced as the Oxford classification. In this study, we aim to evaluate the clinical features and results of our patients with IgAN according to Oxford classification.

Methods: The medical records and the renal biopsy findings of 25 patients with IgAN were retrospectively reviewed. Patients were classified into two groups according to the Oxford classification [(Mesengial hypercellularity score ≤0,5 (MO) above (M1), endocapillary hypercellularity absent (E0) or present (E1), segmental glomerulosclerosis absent (S0) or present (S1), tubular atrophy /interstitial fibrosis ≤25% (TO), 26–50%(T1) or >50% (T2)]. Group 1 (n = 16), MO, EO, S0 and TO; group 2 (n = 9), other. These groups were compared with gender, age of onset, age of diagnosis, mean blood pressure and estimated GFR at diagnosis and follow-up, proteinuria, clinical presentation and prognosis.

Results: The major clinical presentations of our patients were macroscopic hematuria in 23 (92%). A significant difference was not detected between groups for gender, age of onset, age of diagnosis, mean blood pressure and estimated GFR at diagnosis and follow-up, proteinuria, clinical presentation and prognosis.

In conclusion, in this study, we didn’t show that the Oxford classification was applicable to predict the clinical findings and renal outcome in children with IgAN. This may be related to the scarcity number of patients.

PS2-FRI-166

C1Q nephropaty in a 7-year-old boy—a case report

I. Palcic* ¹, M. Cuk¹, A. Cvitkovic Roic², D. Galesic Ljubanovic³, G. Roic¹, Z. Bahtijarevic¹, H. Strizic⁴, J. Delmis¹

¹University Hospital Center “Sestre milosrdnice”, Children’s Hospital Zagreb, Zagreb, Croatia, ²Polyclinic for pediatric diseases Helena, Zagreb, Croatia, ³University of Zagreb School of Medicine Dubrava University Hospital, Zagreb, Croatia, ⁴Health facility Zagreb Center, Zagreb, Croatia

Objectives: C1q nephropathy (C1qN) is a rare glomerular disease characterized by mainly mesangial immunoglobulin and complement deposits, predominantly C1q, with no clinical or serological evidence of systemic lupus erythematosus (SLE). It was first described as a distinct entity by Jennette and Hipp in 1985. Patients with C1qN commonly presented with nephrotic syndrome. But the presentation varies and includes hematuria, hypertension, renal insufficiency, and rarely recurrent gross hematuria.

Methods: We present 7-year-old boy with recurrent episodes of gross hematuria during respiratory infections since he was three years old. His examination was unremarkable and blood pressure was normal. He had persistent microhematuria, no significant proteinuria (up to 300 mg in 24 hour urin collection). Kidney function, as well as immunological tests were normal. There was no family history of renal disease.

Results: A renal biopsy was performed. Light microscopy showed one sclerotic and 31 normal glomeruli. Immunofluorescence demonstrated granular staining for C1q(2+) mostly in capillary loops. Glomerular staining for C3, IgA, IgM, IgG was slightly positive. Electron microscopy revealed segmental mesangial dense deposits. With respect to clinical and laboratory findings for SLE, which were negative, our diagnosis was C1qN.

During three years of regular monitoring his renal function is stable. He has persistent microhematuria without proteinuria or episodes of gross hematuria in the last fifteen months. Complement level is normal and serologic tests for SLE are negative.

Conclusions: Our case report is yet another confirmation that C1qN is distinct entity with various clinical presentation and should be considered in the differential diagnosis of children who present with recurrent gross hematuria.

PS2-FRI-180

The effect of biphosphonates on crystallization in synthetic urine

L. Kovacevic* ¹, H. Lu¹, Y. Lakshmanan¹

¹Children’s Hospital of Michigan, Detroit, USA

Objective: The use of biphosphonates (BP) in the prevention of kidney stones is controversial. We investigated the inhibitory effect of various BP on the crystallization of calcium oxalate monohydrate (COM), calcium phosphate (CaP) and magnesium ammonium phosphate (MAP) in synthetic urine.

Methods: Crystals from synthetic urine were exposed to different concentrations of BP. Urinary turbidity was used as a marker of crystallization and measured by spectrophotometry at 660 nm, based on a validated method in our laboratory. The percent inhibitory activity was calculated using the formula: $\left( {{\text{a}} - {\text{b}}} \right)/{\text{a}} \times {1}00$, (a-baseline maximal turbidity, b-maximal turbidity with various concentrations of medication). Potassium (K) citrate and Magnesium (Mg) citrate were used as positive controls.

Results: The sensitivity of spectrophotometry in measuring turbidity in synthetic urine was confirmed by the linear correlation between the crystal concentration and optical density readings at 660 nm seen on the standard curve. Ibandronate significantly reduced formation of all three types of crystals at very low dose (0.0012 mg/ml), with the strongest inhibitory activity against crystallization of MAP at 1.25 mg/ml (MIA 91%). Risendronate prevented the crystallization of CaP (0.625 mg/ml, MIA 97%), and MAP (2.5 mg/ml, MIA 98%), while Alendronate had good effects on CaOx (0.625 mg/ml, MIA 73%), and MAP (0.625 mg/ml, MIA 94%). Etidronate had similar inhibitory effect on CaOx (MIA 65%), CaP (MIA 68%), and MAP (MIA 71%) at 0.3 mg/ml. Pamidronate did not show any effect on crystallization.

Conclusions: BP are strong inhibitors of crystallization in synthetic urine, with Ibandronate being the most potent one. CaOx crystallization was best prevented by Ibandronate and Alendronate, CaP crystal formation was inhibited by Etidronate and Risendronate, while MAP crystallization was affected by Ibandronate, Risendronate and Alendronate. Further investigation of the use of BP in kidney stone prevention is needed.

PS2-FRI-181

The effect of grape seed extract (GSE) on oxidative stress in puromycin aminonucleoside (PAN)-induced podocyte injury

L. Kovacevic* ¹, H. Lu¹, Y. Lakshmanan¹

¹Children’s Hospital of Michigan, Detroit, USA

Objective: We investigated the effect of GSE on oxidative stress in an in-vitro model of PAN-induced podocyte injury.

Methods: Differentiated murine podocyte clones were treated with a single application of PAN to a final concentration of 5 μg/ml (PAN Group). Controls received an equivalent volume of culture media or GSE. PAN podocytes were treated with GSE at concentration of either 25 μg/ml (G25P Group) or 50 μg/ml (G50P Group). Cells were cultured for an additional 20 minutes, 1 day, 3 days, and 7 days. As markers of oxidative stress we measured the concentrations of superoxide dismutase (SOD) and malondialdehyde (MDA).

Results: GSE significantly improved the viability of PAN treated podocytes on day 5 post-treatment. Podocyte process retraction was noted 7 days after PAN administration, with less pronounced changes seen in the GSE treated group. GSE treatment of PAN-injured podocytes induced higher SOD activity (expressed as inhibition rate %) compared to PAN-injured podocytes alone at all time points; significant increase was noted in G50P Group compared to PAN Group alone at 20 minutes post-treatment (39.3 ± 1.3% vs.4.2 ± 1.5%)(p = 0.005). MDA concentration decreased in PAN injured podocytes treated with GSE compared to PAN treatment alone at all time points; significant decrease was noted in G50P Group compared to PAN Group alone at 7 days post-treatment (43.3 ± 8.4 μM/mg protein vs. 175.1 ± 9.1 μM/mg protein)(p = 0.03).The higher dose of GSE was associated with higher SOD activity (2.8xincrease) and lower MDA concentration at any time point (3xdecrease).

Conclusions: GSE treatment of the PAN-injured podocytes resulted in preservation of cell viability and less alteration of foot processes. GSE induced early increase in SOD activity with subsequent attenuation in lipid peroxidation. Stimulation of antioxidant enzymes by GSE administration appears to be beneficial in the early course of nephrosis, before significant injury is seen. Increased protective effect against the oxidative stress was noted with a higher dose of GSE.

PS2-FRI-182

NPHS1 gene c.349G>A single nucleotide polymorphism (SNP) is not associated with progression of idiopathic childhood steroid-resistant nephrotic syndrome (SRNS)

L. Prikhodina* ¹, O. Ryzhkova², A. Polyakov²

¹Research Institute of Pediatrics & Children Surgery, Moscow, Russian Federation, ²Research Center for Medical Genetics, Moscow, Russian Federation

Objectives: To examine the contribution of SNP c.349G>A of NPHS1, encoding for nephrin, to progression of SRNS to CRF in children.

Methods: Fifty-three children (31F/22M) with primary SRNS were studied. Renal biopsy showed 26 (49%) FSGS, 12 (22%) mesangial proliferative GN (MsPGN), 8 (15%) MPGN, 4 (8%) membranous nephropathy and 3 (6%) MCD. The median age at onset was 9.5 (IQR: 6.0; 13.0) years. The disease duration was 60.0 (36.0; 84.0) months. The follow-up time was 42.0 (24.0; 60.0) months. CRF defined as declining of eGFR <60 mL/min/1.73 m². All 29 exons of NPHS1 were screened by PCR and SSCP analysis in patients and 50 healthy subjects as controls.

Results: NPHS1 SNP c.349G > A was identified in 21/53 (40%) children with SRNS. Allele frequencies and genotype distribution of SNP c.349G > A in patients and controls were consistent with Hardy-Weinberg equilibrium (p > 0.05). Patients with SRNS and c.349G > A NPHS1 in comparison without had no significant differences in the age at onset: 9.0 (5.0; 10.0) vs. 10.0 (7.0; 13.0) years (p = 0.23), duration of disease: 72.0 (48.0; 96.0) vs. 51.6 (36.0; 72.0) months (p = 0.17), frequency of FSGS: 12 (57%) vs. 10 (48%) (p = 0.76; OR = 1.5, 95%CI: 0.4–5.0) and CRF: 5 (24%) vs. 3 (14%) (p = 0.22; OR = 1.9, 95%CI: 0.4–9.1), rate of eGFR decline >4 mL/1.73 m²/year: 13 (62%) vs. 12 (57%) (p = 0.8; OR = 1.2, 95%CI: 0.4–4.2). The 5-year renal survival in patients with SNP c.349G > A NPHS1 versus those without was 83% vs. 73%, 10-year - 67% vs. 47%, respectively (p = 0.38).

Conclusion: There was no association between SNP c.349G > A of NPHS1 and progression of SRNS to CRF in children.

PS2-FRI-183

Predictors of long-term outcome of idiopathic steroid-resistant nephrotic syndrome (SRNS) in children

L. Prikhodina* ¹, V. Dlin¹, M. Ignatova¹

¹Research Institute of Pediatrics & Children Surgery, Moscow, Russian Federation

Objectives: To identify independent predictors of CRF in children with idiopathic SRNS.

Methods: 120 children (52M/68F) with primary SRNS were retrospectively studied. Renal biopsy revealed 53 (44%) FSGS, 28 (23%) mesangial proliferative GN, 19 (16%) membranoproliferative GN, 14 (12%) MCD, 6 (5%) membranous nephropathy. The median age at onset was 9.5 (IQR: 5.3;13.0) years. The disease duration was 48.0 (28.2;72.0) months. The risk of CRF was defined as declining of eGFR <60 mL/min/1.73 m².

Results: 26 (22%) children with SRNS progressed to CRF during the follow-up. The renal survival at 5 and 10 years was 82% and 56%. The univariate analysis revealed significant predictors of CRF in SRNS: increased serum creatinine level at presentation (p = 0.018; HR = 2.6, 95%CI: 1.2–5.9), hypoalbuminemia <25 g/L associated with proteinuria >1 g/d after failing of initial steroids (p = 0.001; HR = 5.2, 95%CI:1.9–14.5), proteinuria >5 g/1.73 m²/d (p = 0.001; HR = 4.0, 95%CI:1.8–9.1), stage 2 hypertension (p = 0.001; HR = 3.9, 95%CI:1.8–8.5), FSGS (p < 0.0001; HR = 7.4, 95%CI:2.5–21.8), rate of eGFR decline >15 mL/1.73 m²/year (p < 0.0001; HR = 11.8, 95%CI:4.7–29.6), no response to immunosuppressive treatment (p = 0.006; HR = 8.0, 95%CI:1.8–35.3). The rate of eGFR decline >15 mL/1.73 m²/year was the only independent predictor of CRF in SRNS in a multivariate analysis using Cox regression model (p < 0.0001).

Conclusion: Children with idiopathic SRNS with declining of eGFR >15 mL/1.73 m²/year have the highest risk of progression to CRF.

PS2-FRI-188

A case report of efficiency of plasma exchange in treatment of goodpasture’s syndrome

Y. Shen* ¹

¹Beijing children’s hospital afflicted to capital institute of medicine, Beijing, China

Objective: Goodpasture’s syndrome(GPS) is an autoimmune disease that has rarely been described in children. Plasma exchange (PE) has been used in the therapy of a wide variety of disorders. To investigate the efficiency of PE in treatment of GPS in children.

Methods: We reported a case of GPS that treated with PE combined with immunosuppression therapy. The patient was a 15-year-old teenager with the main complaints of intermittent fever with coughs 45 days and oliguria 6 days. She had blood-streaked sputum 2 times.Laboratory f indings showed: hemoglobin (Hb) 85 g/L; Creatinine 863.1 umol/L , BUN 16.85 mmol/L. GPS was diagnosed because the patient was negative for MPO-ANCA and PR3-ANCA, but positive for anti-GBM antibodies. The titer of anti-GBM antibodies was above 200 RU/mL. Pulmonary hemorrhage was diagnosed on fiexible bronchofiberscope. Renal biopsy showed sclerosing glomerulonephritis.

Result: Hemodialysis, immunosuppression therapy (methylprednisolone and cyclophosphamide) and PE were performed. Anti-GBM antibodies were followed pre- and post-PE. The antibody levels were above 200 and 184 RU/mL before and after the first PE procedure, respectively. After 4 PE procedures, the level before PE was below 200 RU/mL. Subsequently, the removal efficiencies were 85%, 82% ,55%, 22% and15% after the fifth, sixth, seventh, eighth and ninth PE procedures. For The serum anti-GBM antibody concentrations decreased from pre- to post-PE, indicating that PE may be an effective therapeutic approach in GPS. After the treatment of PE, hemodialysis, pulse methylprednisolone followed by oral prednisone, cyclophosphamide, pulmonary hemorrhage resolved, but renal function did not improve and she continued to require intermittent hemodialysis.

Conclusion: GPS is characterized by pulmonary hemorrhage, rapid progressive glomerulonephritis and the presence of anti-GBM antibodies. PE is an effective method for GPS.

PS2-FRI-192

Control of cyclosporine a treatment in children with steroid-resistant and steroid-dependent nephrotic syndrome

M. Matveeva* ¹, L. Leonova², A. Kucherenko³, T. Vashurina¹, O. Zrobok¹, A. Tsygin¹

¹Nephrology department, NCZD Centre for children health, Khimki, Russian Federation, ²Pathology laborotory, NCZD Centre for children health, Khimki, Russian Federation, ³Pathophysiology laborotory, NCZD Centre for children health, Khimki, Russian Federation

Objectives and study: The aim of this study was to establish cyclosporine A (CsA) average dose necessary to remission achievement and prednisolone withdrawal in children with steroid-resistant nephrotic syndrome (SRNS) and steroid-dependent nephrotic syndrome (SDNS) respectively.

Methods: 30 patients with nephrotic syndrome (18 with SRNS and 12 with SDNS; 6 with focal and segmental glomerulosclerosis and 23 with minimal change disease) with CsA treatment up to 48 months were examined. CsA treatment in children with SDNS was begun in remission. The serum level of CsA was measured by fluorescent polarization immunoassay before morning uptake of the drug (C0) and 2 hours after (C2).

Results: We found that CsA average dosage for remission achievement in children with SRNS was 4,037 mg/kg/day (±1,11), C0 132 ng/ml (±171), C2 820 ng/ml (±346). The dosage for safe prednisolone withdrawal was 4,157 mg/kg/day (±0,81), C0 117 ng/ml (±74), C2 710 ng/ml (±182). The differences between 2 groups were not significant. The dosages and concentrations for remission maintenance were 3,29 mg/kg/day (±1,64), C0 71 ng/ml (±49), C2 612 ng/ml (±246) for SRNS and 3,28 mg/kg/day (±0,84), C0 72 ng/ml (±28), C2 489 ng/ml (±233) for SDNS. The average duration of remission for SRNS and SDNS was 24 months (±13) and 22 months (±8) correspondingly. In 6 children with SRNS CsA was withdrawn after 34 months (±10) of CsA treatment without relapses during 6 month follow-up period.

Conclusions: The monitoring of serum CsA concentration is an efficient tool for building a treatment strategy for SRNS and SDNS in children. C2 is less variable, so it is more reliable.

PS2-FRI-199

Unusual case of extreme hypercalciuria in infancy

M. Ćuk* ¹, I. Palčić¹, O. Žaja-Franulović¹, T. Lesar¹

¹Division of Pediatric Nephrology, Depertment of Pediatrics, University Hospital Center “Sisters of Charity”, Zagreb, Croatia

Osteopeny of prematurity is metabolic bone disease characterized by low mineral bone density due to inadequate phosphorus and calcium intake after the birth, and inadequate capability of premature infant to absorb them in intestine and reabsorb them in tubules. Here we report a case of metabolic bone disease due to prematurity that was expressed in infancy. Male infant referred to our department at the age of 6 month because of suspected tubulopathy. He was born after uncontrolled pregnancy in 32nd week. Family history unremarkable. Birth weight 1780 g, length 43 cm. Due to the anemia he received transfusion. He was fed with extensive hydrolizate due to suspected allergy to the cow’s milk protein and was on rickets prophylaxis with cholecalciferol, 800 U/day.

After discharge, at the age of 2–3 months he was hospitalized on several occasions because of gastrointestinal and respiratory tract infection. In laboratory findings there was hypercalcemia, calcium (Ca) 2,4–2,63 mmol/l, elevated alkaline phosphatase (ALP) 641 U/l, and PTH 149 pg/ml; phosphorus (P) wasn’t measured at that time.

When he was 6 month (BW 3,7 kg <3 c, BL 51 cm <3 c) laboratory findings were: P 0,92 mmol/l, Ca 2,78 mmol/l, ALP 917 U/l—due to bone isoenzyme, PTH, ABS and other laboratory findings were unremarkable. He had extreme hypercalciuria, and immeasurable urine phosphorus (spot urine Ca/creatinine 6,7 mmol/mmol), 24-h urine Ca 0,67 mmol/kg and other elevated markers of bone activity Beta—cross laps and osteocalcin.

Alpha 1 microglobuline, glucose in urine and other test of tubular function were normal. The knee X ray showed osteopeny with significant periostal reaction.

The phosphorus replacement was started along with cholecalciferol. After 2 months of treatment laboratory findings were: Ca 2,45, P 2,14 mmol/l, spot urine: Ca/creatinine 0,12 mmol/mmol, TmPi/GFR 2,1 mmol/l.

PS2-FRI-200

Combination of cyclosporine A and mycophenolat mofetil in experimental nephrotic syndrome

A.Sülü¹, H. Akbas², B. Kilicarslan Akkaya³, E. Comak⁴, A. Uslu Gökceoglu⁴, C.S. Dogan⁴, M. Koyun⁴, S. Akman* ¹

¹Akdeniz University, Medical Faculty, ²Department of Pediatrics, Akdeniz University, Medical Faculty, Department of Biochemistry, ³Akdeniz University, Medical Faculty, Department of Pathology, ⁴Akdeniz University, Medical Faculty, Department of Pediatrics, Division of Pediatric Nephrology

Aim: To compare the efficiency of combined and separate usage of mycophenolat mofetil (MMF) and cyclosporine A (CsA) in experimental nephrotic syndrome (NS).

Method: 50 rats, that had developed NS by administering adriamycin, were divided into 5 groups: control, CsA, MMF, low-dose CsA and combined therapy (low-dose CsA + MMF). Blood and urine were collected at 0, 4th and 8th week to measure protein, creatinine, albumin, cholesterol, triglyceride, total anti-oxydant status, total oxydant status and oxydative stress index (OSI). At the end of the study, rats were sacrificed; kidney tissues were stained by hematoxylene eosin, masson trichrom, TGF β and osteopontin (OPN) to calculate interstitial fibrosis score (IFS), total damage score (TDS) and glomerulosclerosis index (GSI).

Results: At the 4th week, serum creatinine was lower and plasma total protein was higher in MMF group compared to CsA group, whereas serum creatinine was higher in CsA group than that of low-dose CsA and combined therapy groups (p = 0,007, p = 0,028). Also, OSI was lower in low-dose CsA than CsA and combined therapy groups. At the 8th week, proteinuria regressed compared to 4h week in both MMF and low-dose CSA groups, whereas plasma total protein levels were higher in combined therapy than that of CsA and MMF groups (p = 0.044, p = 0,031), and in low-dose CsA compared to MMF group. For histopathological analysis, GSI and TDS were higher and OPN was lower in CsA group than all other groups; IFS were higher in MMF compared to combined therapy group, whereas TGFβ was higher in MMF compared to CsA group.

Conclusion: It seems that combination therapy of CsA and MMF is more effective than separate usage of both agents to protect renal function and serum total protein in experimental nephrotic syndrome.

PS2-FRI-202

Strategies for use of rituximab in refractory nephrotic syndrome

W. Hayes* ¹, M. Christian¹

¹Children\’s Renal and Urology Unit, Nottingham, UK

Objectives and study: We performed a casenote review of patients in our centre who received rituximab between 1/1/08 and 28/2/11 for nephrotic syndrome (frequently relapsing and/or steroid dependent [n = 17], steroid resistant [n = 1], relapse post-transplant [n = 1]). Differing treatment strategies were used, including: 1. Single dose (11 patients) versus repeat dosing (8 patients)

2. Of those receiving repeat doses: regular repeat dosing (3 patients) versus awaiting B-cell repopulation (5 patients) 3. Continuation of baseline immunosuppression (6 patients) versus reduction when B-cell deplete (13 patients) Rituximab (375 mg/m2/dose) was given to 19 patients at a median age of 13.1 y (3.1–18.2 y). Hypotension during infusion occurred in one patient. Median follow up was 326 days (32–1014 days).

Results: In patients treated with multiple doses, median annualised relapse rate fell from 4.5(1–6) to 1.7(1.5–2). In patients treated with a single dose, excluding 3 patients whose persistent nephrotic state was unresponsive to rituximab, median annualised relapse rate fell from 3.0(2.8–4.6) to 0(0–2.4). Three patients showed no response to rituximab. Three patients relapsed with B cell repopulation. In 13 patients baseline immunosupression was successfully weaned including prednisolone in all 13 and tacrolimus in 9 patients. Two patients have exhibited increased responsiveness to steroid and tacrolimus beyond B cell repopulation.

Conclusions: Not all patients benefit from rituximab however in our series, single-dose rituximab was effective in sustaining remission. In some patients rituximab may also exhibit a disease-modifying effect following B cell repopulation. Registries and multi-centre studies are urgently needed that will predict patients likely to respond, to individualise the most effective strategy and to document the long-term risks.

PS2-FRI-207

Juvenile systemic lupus erythematosus (JSLE) in Croatia—a national study over the past 20 years

A. Lukić* ¹, M. Jelušić-Dražić¹, D. Batinić¹, D. Milošević¹, K. Vrljičak¹, V. Rožmanić², M. Šuvat-Dežulović², M. Saraga³, L. Stričević³, I. Malčić¹

¹Department of Paediatrics, University Hospital Center Zagreb, Zagreb, Croatia ²Department of Paediatrics, University Hospital Center Rijeka, Rijeka, Croatia ³Department of Paediatrics, University Hospital Center Split, Split, Croatia

Aim: To analyze cumulative clinical and laboratory features, and outcome of Croatian children with JSLE, followed between 1987 and 2009.

Results: Of 85 children, there were 73 girls and 12 boys, with mean age at disease onset, years ± SD (range), 13.0 ± 2.84 (6–18). The youngest girl was 6, and the youngest boy was 7 years old. The symptoms were present on average 3 months (range 0–96 months) before the diagnosis was made. The commonest presenting clinical features were arthralgias (79%), skin (66%), constitutional (65%), renal (58%), cardiac (21%), and CNS (16%). Proteinuria was present in 57% of cases, but renal biopsy revealed lupus nephritis in 29 (34%) children: class II in 6% class III in 28%, class IV LN 28%, class V in 21%, and class VI in 17% cases. The patients presented significantly altered laboratory parameters including high ESR (91%), some sort of cytopenia (73%), deficiency of complement C3 (62%) and C4 (38%), low total haemolythic complement activity (54%), and circulating immunocomplex (77%). Children had positive antinuclear and other antibodies: anti-dsDNA (74%), anti-SS-A (28%), anti-SS-B (23%), anti-Sm (69%), anti-RNP (44%), anti-Sc70 (40%), anit-histons (83%), aCL-IgM (61%), aCL-IgG (79%), RF (48%); while 65% of them had high IgG levels, and AST-O titre (35%). Five patients (6%) also had primary immunodeficiency (selective IgA deficiency). There was no difference in clinical or laboratory features between boys and girls, or depending on the age of disease onset. During the study period two patients died, one because catastrophic antiphospholid syndrome, other because of terminal renal failure.

Conclusion: There is no significant difference in clinical, immunopathological features and therapy regimens in our patients compared to those in most paediatric SLE studies.

PS2-FRI-208

Thin basement membrane nephropathy in children and adolescents: 22 years’ experience of a tertiary center in Portugal

L. Correia-Costa* ¹, H. Pinto¹, C. Tavares¹, A. Teixeira¹, A. Caldas Afonso¹

¹Nephrology Unit, Pediatrics Department, Hospital de S. João, E.P.E—Oporto, Portugal

Objectives/study: Thin basement membrane nephropathy (TBMN) is the most common cause of persistent glomerular hematuria. The disease may not always have a benign course because of misdiagnosed conditions, namely X-linked Alport Syndrome or coincidental renal diseases. We aimed to evaluate epidemiology, clinical features and outcome of patients with biopsy proven TBMN.

Methods: We reviewed medical records of all pediatric patients over the last 22 years in whom renal biopsy showed diffuse thinning of glomerular basement membrane at ultrastructural examination. Follow-up data analyzed included urinalysis, blood pressure and glomerular filtration rate (GFR).

Results: Eleven patients were included (63,6% female), aged 3–10 years at time of presentation. Familial history of TBMN was positive in only one patient. Nine patients presented with microscopic persistent hematuria; 1 had recurrent episodes of macroscopic hematuria and 1 had hematuria associated to mild proteinuria. Renal biopsy was performed 1 to 7 years after presentation. Light microscopy and immunofluorescence revealed no changes in nine patients and slight mesangial cellularity in two. Follow-up data were available for 9 patients (between 6 months and 13 years after biopsy). All of them maintained persistent microscopic hematuria and two patients developed microalbuminuria that remitted with angiotensin-converting enzyme inhibitor treatment. All patients maintained normal blood pressure and GFR >90 ml/min/1.73 m². None presented any of the typical features of Alport syndrome.

Conclusions: Our patients had a favorable evolution despite appearance of microalbuminuria. TBMN is probably underdiagnosed due to hematuria being incidentally found and controversial biopsy criteria in children without other abnormal signs. Patients with TBMN should be routinely monitored for proteinuria, hypertension and GFR decrease due to possibility of disease progression. Immunohistochemical study of renal tissue for collagen IV alpha-chains and genetic analysis for COL4A3 and COL4A4, if routinely available, could be of great value for differential diagnosis, affecting genetic counseling and risk ascertainment.

PS2-FRI-209

Evaluation of renal ιinvolvement in children and adolescents with sickle/beta thalassemia of greek origin

N. Printza* ¹, E. Papadopoulou¹, M. Economou¹, E. Teli¹, V. Tzimouli¹, E. Farmaki¹, N. Gompakis¹, M. Athanassiou-Metaxa¹, F. Papachristou¹

¹1st Pediatric Departement, Aristotle University, Hippokration General Hospital, Thessaloniki, Greece

Objectives and study: Few studies have assessed parameters of renal involvement in patients of young age with sickle cell disease (SCD), while relative literature in sickle/beta-thalassemia (S/b-thal) patients is even more limited. We aimed to evaluate the renal function in children and adolescents with sickle/beta-thalassemia of greek origin.

Methods: Seventeen S/b-thal patients, aged 3.5 to 18 years (mean 10.97 ± 4.87 years) were evaluated. Mean haemoglobin (Hb) level was 9 ± 0.7 g/dl. None of the patients was recently hospitalized, was on hydroxyurea or a chronic transfusion program, nor presented additional risk factors for renal disease. In addition to conventional renal biochemistries, estimated glomerular filtration rate, serum cystatin C (Cys C), fractional excretion of sodium (FENa), tubular phosphorus re-absorption and urine calcium, protein, microalbumin and β2 microglobulin (β2 MG) were measured. Moreover renal ultrasound was performed.

Results: Mean eGFR was 142.2 ± 22.5 ml/min/1.73 m², with approximately half of the patients (8/17) presenting with an eGFR >150 ml/min/1.73 m². Mean urine specific gravity was 1011.3 ± 3.9. No patient presented with microscopic hematuria or with hypercalciuria. Biochemical urine analysis revealed normal sodium excretion and phosphate re-absorption. In all patients serum Cys C and urine β2 MG levels were within normal range. However, 29.4% of patients (5/17) demonstrated impaired glomerular function with proteinuria or microalbuminuria (11.8% and 17.6%, respectively). Regression analysis revealed no correlation between age, annual number of vaso-occlusive crisis, Hb, HbF, eGFR, LDH, Cys C or β2 MG levels with the presence of proteinuria or microalbuminuria. Renal ultrasound was normal in all cases.

Conclusions: Our study revealed a considerably high rate of proteinuria and microalbuminuria in the young S/b-thal group studied. Given that glomerular damage seems to develop early and irrespective of pain rate in S/b-thal patients, it is recommended that regular testing of relative markers is performed in this patient group.

PS2-FRI-221

Epidemiological characteristic of childhood vasculitides: a retrospective study over the last 10 years

M. Jelušić-Dražić*¹, I. Malčić¹, D. Batinić¹, M. Milošević¹, K. Vrljičak¹, Lj. Nižić¹, M. Vikić-Topić¹, K. Starčević¹, B. Malenica²

¹Department of Paediatrics, University Hospital Centre, Zagreb University School of Medicine, Zagreb, Croatia, ²Division of Immunology Clinical Institute of Laboratory Diagnosis, University Hospital Centre, Zagreb University School of Medicine, Zagreb, Croatia

Introduction: Vasculitis syndromes comprise a heterogeneous group of disorders sharing the hystopathologic features of inflammation and necrosis in blood vessels, which can lead to tissue damage.

Aim: To analyze characteristics of the presenting and cumulative clinical features, laboratory features, treatment modalities, disease activity and outcome of children with vasculitis.

Methods: All patients aged from 1 to 18 years and diagnosed during the period 1998–2010 at Department of Paediatrics, University Hospital Centre Zagreb, Croatia, as having vasculitis according EULAR/PRES criteria were enrolled into the study.

Results: There were 182 children diagnosed as having vasculitis, 90 girls and 92 boys, with the mean age at disease onset (±SD) 10.08 ± 3.53 years. Henoch-Schonlein purpura was present in 126 patients (69,2%), cutaneous leucocytoclastic vasculitis in 16 (8,8%), polyarteritis nodosa in 12 (6,6%), vasculitis associated with connective tissue diseases in 10 (5,5%), hypersensitivity vasculitis in 12 (6,6%), and Kawasaki disease in 6 (3,3%). White cell count, ESR and CRP were mildly elevated in the most patient. Antistreptolysin O was elevated in 127 patients (69%). Antineutrophil cytoplasmic antibodies were positive in only 6 patients (3,3%). No relation was found between the severity of skin involvement and involvement of other organs. Supportive measures of treatment in the form of non-steroidal inflammatory drugs were the mode of treatment in the majority of patients, while patients with organ involvement were treated with corticosteroids, immunosuppresives, immunoglobulines intravenously, plasmapheresis and rituximab. During the follow-up, two patients with mycroscopic polyangiitis died due to chronic renal failure and one patient developed intestinal perforation.

Conclusion: Comparing to American, European and Turkish studies we found a difference in the distribution of childhood vasculitides, while clinical, laboratory features and therapy regimens were similar.

PS2-FRI-222

Tacrolimus as adjuvant therapy in nephrotic syndrome—a single centre experience

M. Muorah¹, D. Simpson¹, J. Booth¹, M. Ognjanovic¹, Y. Tse* ¹

¹Great North Children\’s Hospital, Newcastle Upon Tyne, UK

Objective: To assess outcome of children treated with tacrolimus for nephrotic syndrome.

Method: Retrospectively case note and biopsy review from children who received tacrolimus +/− additional mycophenolate mofetil (MMF) to treat nephrotic syndrome.

Results: From 2002–2010, 30 children were treated with tacrolimus. Median age at presentation 2.7 years (1.2–11.5), 29 (97%) Caucasian and 17 (57%) male. 19 (63%) were steroid sensitive within 28 days (SSNS) with an additional two responding at 65 and 94 days. Histological diagnoses were 5 (17%) focal and segmental glomerular sclerosis, 22 (73%) minimal change disease and 3 not biopsied. Prior second line treatment included a varied combination of: 23 (76%) cyclophosphamide, 9 (30%) levamisole, 2 (7%) ciclosporin while 5 (17%) received steroids alone. Tacrolimus was started in SSNS at median 25 (4–182) and in SRNS at 5 (1–12) months post presentation. Number of relapses in SSNS group were 3.5 vs. 1.6 per year before and after tacrolimus treatment respectively (p < 0.001).

Followed up was median 44 months (3–84) post-tacrolimus. Twelve patients had surveillance biopsies at median 47 (21–75) months. One case of global sclerosis was found at 54 months post-tacrolimus on repeated biopsies with eGFR 124 ml/1.73 m²/min. Median eGFR was 111 ml/1.73 m²/min (range 74–161) for all other patients.

Fourteen (1–85) months after starting tacrolimus, seven (23%) patients remain steroid free. Sixteen of 23 remaining patients were commenced on MMF at 44 (3–76) months post-tacrolimus. Five became steroid free.

Conclusion: Children receiving tacrolimus to treat nephrotic syndrome have reduced frequency of relapses whilst maintaining a stable GFR. Tacrolimus may provide an adequate alternative to ciclosporin with less cosmetic side effects. The majority of patients required further treatment. MMF was an effective adjuvant in some patients.

PS2-FRI-229

An immune mediated glomerulonephritis in association with WAGR syndrome

D. Noone*¹, S.D. Marks¹, N.J. Sebire²

¹Department of Paediatric Nephrology, Great Ormond Street Hospital for Children, London, UK ²Department of Paediatric Pathology, Great Ormond Street Hospital for Children, London, UK

Objectives and study: WAGR (Wilms’ tumour, aniridia, genitourinary anomalies, and mental retardation syndrome) is a contiguous gene syndrome resulting from a deletion at chromosome 11p13. WT1 expression in the adult kidney is in the podocytes and syndromes associated with WT1 mutations are known to be associated with focal and segmental glomerulosclerosis (FSGS) and diffuse mesangial sclerosis (DMS). We report a thirteen year old male with WAGR syndrome who presented with hypertension, albuminuria and microscopic haematuria and had an immune mediated glomerulonephritis confirmed on renal biopsy.

Case report: A thirteen year old male with genetically confirmed WAGR syndrome was referred for the assessment of hypertension with systolic blood pressure of 150 mmHg. He had 2+ proteinuria and 3+ haematuria with urine albumin:creatinine ratio elevated at 600 mg/mmol. He had mild anaemia, a neutrophil leucocytosis with elevated CRP of 56 mg/l and elevated ESR of 68 mm/hr. He had normal renal function (creatinine = 48 μmol/l) and albumin of 37 g/l. He had normal complement C3 and C4 with negative ANA and ANCA . Renal biopsy showed features of an atypical complex immune-mediated glomerulonephritis with mixed mesangial proliferative, endocapillary proliferative and membranoproliferative features in addition to focal segmental scarring. Immunostaining showed granular positivity for IgA, IgM and C1q. Electron microscopy revealed focal podocyte foot process effacement and extensive mesangial electron dense deposits without subendothelial or subepithelial deposits. His immune-mediated glomerulonephritis was treated with MYCOPHENOLATE MOFETIL AND ENALAPRIL.

Conclusions: This case reports the unusual association of an immune mediated glomerulonephritis in a patient with WAGR syndrome. Reduced expression of WT1 has been shown in a mouse model to result in both a crescentic glomerulonephritis and mesangial sclerosis. WT1 mutations could be associated with a glomerulonephritic process that may account for the increased risk of renal impairment. Patients with WAGR should be clinically monitored for evidence of renal involvement.

PS2-FRI-237

A single center experience of proteinuria

K. Losonczi*¹, I. Bajusz¹, L. Szabo^1,2,3

¹Department of Pediatric Nephrology, Velkey László Child Health Centre, Borsod County Teaching Hospital, Miskolc, Hungary, ²Department of Health Science, University of Miskolc, Miskolc, Hungary, ³Postgraduate Institute of Pediatrics, University of Debrecen, Miskolc, Hungary

Proteinuria can be identified as either a transient or a persistent finding and can represent a benign condition or a serious disease.

During a 10-year period, 122 children with proteinuria were examined at the Department of Pediatric Nephrology of the Child Health Center of Borsod County Teaching Hospital. 53 children had proteinuria and hematuria, and 69 patients had only proteinuria. 14 patients had proteinuria without edema. They ages ranged from 9–16 years. 9 of them had orthostatic proteinuria. 4 of them had proteinuria followed by fever. 1 patient had proteinuria without any other symptoms. Nephrotic syndrome was established in 55 patients. The ages of the patient ranged from 1 to 13 years, the average age was 3.52 years at the onset of nephrotic syndrome. 39 of them was boy. One child had congenital nephrotic syndrome, 52 children had steroid sensitiv nephrotic syndrome, and 40 of them had relapsing nephrosis. Two patients had steroid resistant nephrotic syndrome. Renal biopsy was taken in 16 patients. 1 had congenital nephrotic syndrome, 4 children had minimal change disease, but one of them was the steroid resistant nephrotic patient. 2 other patients had focal segmental glomerulo sclerosis, 2 patients had mesangioproliferativ glomerulonephritis, 1 child had IgA nephropathy, 1 had mesangiocappilary nephropathy, and 5 had IgM nephropathy. The inicial treatment was steroid in each patient. Cyclophosphamide was given in 25 pts, Cyclosporin A in 15 pts, and two patient was treated by levamisol.

Only in one case developed chronic renal failure, who had congenital nephrotic syndrome, and he was treated by peritoneal dialysis and finaly transplanted. All of them are well.

PS2-FRI-239

Anti-glomerular basal membrane antibody glomerulonephritis—case report

S. Collopy*¹, L. Henriques¹, D. Malheiros², V.M. Koch¹

¹Instituto da Criança, Clinics Hospital—Medicine School of São Paulo University, São Paulo, Brasil, ²Pathology Service—Clinics Hospital—Medicine School of São Paulo University, São Paulo, Brasil

Objectives: Present a rare case of glomerulonephritis with unfortunate outcome. methods:charts review of clinical, laboratory and imaging exams data.

Results: A previously healthy 12 year old girl with a history of acute non-bloody gastroenteritis presented at the emergency room with severe acute renal failure and the need of renal support. She had no personal or family history of renal pathologies, inflamatory or rheumatological diseases. Rheumatological and inflamatory tests showed negatives. The ultrasound revealed small kidneys with loss of the cortical-parenchyma relation. She presented microalbuminuria, microhematuria, mild hypertensive retinopathy and left ventricule concentric hypertrophy. renal substitution therapy was started immediatelly and a surgical biopsy revealed a necrotizing crescentic glomerulonephritis with positive linear pattern and global and diffue distributtion imunofluorescence for imunoglobulines. Seric anti-glomerular basal membrane antibody (Ac anti-GBM) was 59 μg/ml. As therapeutic treatment was used:3 metilprednisolone (MTP)pulses (30 mg/kg) followed by prednisone 60 mg/day and plasmapheresis (14 sessions). As the seric Ac anti-GBM was 19 μg/ml after the 5th session, a cyclophosphamide (CYA) pulse was performed (500 mg/m2). No satisfatory clinical response was achieved after the 10th session and progressive platelet fall developed. 3 MTP pulses was repeated and mycophenolate mophetil (MM) iniciated. A few days after the plasmapheresis sessions ended, the patient presented with tonic-clonic seizure so another CYA and MTP pulses were instituted and MM was discontinued as the platelet count remained low. Cranial CT and electroencephalogram were normal. 3 days later, another seizure occured asoociated with severe cerebral haemorrhage wich led the patient to death.

Conclusions: Refractory case to classical treatment of plasmapheresis and imunosupression with corticosteroid and cyclophosphamide wich severity and final outcome were not related to the main death cause in these cases—pulmonary haemorrhage. the cerebral bleeding may suggest vasculitis or systemic disease associated.

PS2-FRI-241

Nephrotic syndrome, central venous line (CVL), and intracardiac thrombus requiring surgical treatment

P. Yadav* ¹, M. Ognjanovic¹, Y. Tse¹, J. Booth¹, D. Simpson¹

¹Department of paediatric nephrology,Great North children Hospital,Newcastle upon tyne, UK

Objective: Over 50% of VTEs in children occur in the upper venous system secondary to the use of central venous lines (CVLs). Nephrotic syndrome with its inherent prothrombotic state increases this risk manyfold. To highlight that CVL placement in these high risk group can be potentially devastating and using thromboprophylaxis should not make us complacent.

Methods: We report a 2 year old girl who presented to us with difficult to treat nephrotic syndrome .In her 2 months of hospitalisation she needed multiple albumin infusions .As access was problematic she had a central line inserted ,following which was started on daily prophylactic Tinzaparin in view of her prothrombotic state (relative immobility,gross oedema and profound hypovolemia).She underwent a renal biopsy which showed minimal change disease with early changes of FSGS. At this point she was started on Tacrolimus with good effect and discharged as she was less proteinuric and no longer albumin dependent.

Results: She represented a week later with swelling of her face and arm and an echo cardiogram showed thrombus in the right internal jugular extending into right atrium .She was initially treated with heparin infusion but eventually had a surgical thrombectomy to remove the thrombus.

Conclusions: CVL-related TEs are not trivial as they require repeat anesthesia for CVL placement, provide a source for PE cause superior vena cava syndrome , chylothorax and eventual destruction of the upper venous system and contribute to post-thrombotic syndrome (PTS)in both upper and lower extremities.

Inspite of thromboprophylaxis our patient developed thrombosis which could have been fatal.We need to carefully weigh the risk and balance our judgment when placing these lines in this high risk cohort.

PS2-FRI-244

The influence of treatment on clinical outcome in mild and moderate forms of Henoch-Schoenlein purpura nephritis

B. Kasap*¹, E. Kose², C. Alparslan², A. Bal², O. Yavascan¹, N. Aksu¹

¹Tepecik Research and Training Hospital Division of Pediatric Nephrology, Izmir, Turkey ²Tepecik Research and Training Hospital Department of Pediatrics, Izmir, Turkey

Aim: Treatment strategies in Henoch-Schoenlein purpura nephritis (HSPN) are globally controversial. We aimed to investigate the outcome of different treatment options at different grades of HSPN.

Patients and methods: The data of patients diagnosed with HSPN between 1994 and 2011 were reviewed retrospectively. Their gender, age at the time of diagnosis, involvement of skin, joints and gastrointestinal system, presence of hematuria and proteinuria, both at the time of diagnosis and at the end of follow-up, and treatment modalities were recorded. The histopathological findings were graded according to the ISKDC classification and two groups were formed as mild (Group1:Grades 1&2) and moderate (Group2:Grades 3&4). The parameters were compared between the two groups.

Results: There were 25 patients (M/F:15/10) with a mean age of 98.4 ± 30.16 months. All had purpuric lesions. There were joint involvement in 48%, gastrointestinal system involvement in 36%, hematuria in 72% and proteinuria in 64% of the patients at the time of diagnosis. Twenty-eight percent (n:7) received pulse steroid followed by oral steroid, 32% (n:8) received oral steroid without pulse treatment. Sixty percent (n:15) of the patients received ACEI in combination with steroids (n:12) or alone (n:3). None of the patients received other immunosuppressants. There were 16 patients in Group1 and 9 patients in Group2. Age, gender, system involvement, hematuria and proteinuria incidences and GFR, intensity of IgA accumulation at the time of diagnosis, and treatment modalities were similar between the two groups (p > 0.05). Three patients were lost to follow-up. Treatment duration was significantly longer in Group2 (p:0.044). Hematuria insisted in 3 of 11 patients in Group1. Hematuria in Group2 and proteinuria in both groups disappeared at the end of the follow-up.

Conclusion: Since the clinical outcomes were similar in both groups as a result of similar treatment options, we may conclude that moderate forms of HSPN may also be treated as mild forms.

PS2-FRI-245

Urinary NAG activity in chldren with urolithiasis

N. Yildiz¹, M. Benzer*¹, O. Baykan², R. Fırat², U. Altuntas1, H. Alpay¹

¹Marmara University Faculty of Medicine, Department of Pediatric Nephrology, Istanbul, Turkey ²Marmara University Faculty of Medicine, Department of Biochemistry, Istanbul, Turkey

The aim of our study was to evaluate tubular dysfunction in children with urolithiasis (UL) by measuring urinary N acetyl glucosaminidase (NAG) activity and creatinine (Cr) levels.

Patients and methods: Forty-two (27 girls, 15 boys) children with UL followed-up in our unit and 25 healthy controls with similar age and gender were enrolled into the study. The patients with chronic renal failure or any tubular disease were excluded.

Serum and urine electrolytes (Na, K, Ca, P), creatinine, urinary excretions of beta 2-microglobulin (beta 2-MG) and NAG activity were measured. The urinary NAG activity was measured using a colorimetric method and the results were expressed as molar creatinine (Cr) ratios. Estimated glomerular filtration rate (eGFR) was calculated by Schwartz formula.

Results: The mean ages of the patients and control group were 8.2 ± 4.4 (1.4–18.3) and 6.6 ±2.42 (2–11) years respectively. The mean age at the presentation was 5.1 ± 4.2 (0.4–16.5) years for children with UL. Serum and urinary electrolytes and eGFR were similar in two groups. The mean urinary NAG/creatinine ratios of the patients and the control group were 0.04 ± 0.02 and 0.02 ± 0.02 respectively. The difference between two groups was significant (p < 0.001). There were no significant relation between NAG/creatinine ratio and urinary oxalate, citrate, uric acid, calcium levels in patients with UL.

Conclusions: Higher urinary NAG activity with normal excretion of electrolytes may be the evidence of persistent although slight proximal tubular dysfunction in children with UL. Hyperoxaluria, hypocitraturia, hyperuricosuria and/or hypercalciuria did not correlate with urinary NAG activity. Long-term follow-up may be important to determine the possible mild electrolyte disturbances secondary to tubular dysfunction in later life.

PS2-FRI-252

Acute intermittent porphyria (AIP), hypertension and hyponatremia

P. Yadav*¹, M. Ognjanovic¹, Y. Tse¹

¹Department of paediatric nephrology,Great North children Hospital, Newcastle upon tyne, UK

Objective: To highlight acute presentation of porphyria to a renal unit with hyponatremia and hypertension

Methods: A 15 year old girl referred to the renal team with hyponatremia and hypertension. In the past she has had had two admissions for lower abdominal and back pain and dark urine. On the first admission she also had seizures. Serum sodium was 119 mmol/l. Hyponatremia responded to fluid restriction. The patient had longstanding depression and was on fluoxetine. Her hyponatremia was attributed to fluoxetine induced SIADH. Hypertension was treated with amlodipine. Systemic examination was unremarkable. Review of history revealed close correlation between abdominal pain and hyponatremia, constipation and menstrual cycle and dark coloured urine.

Results: Investigations for hyponatremia suggested SIADH. Further investigations showed normal cortisol and thyroid function. Clinical diagnosis of porphyria was made. The porphyria screen was positive. The family history revealed her maternal aunt has been having identical symptoms/signs for many years .

Conclusions: AIP is an autosomal dominant disease resulting from deficient PBG deaminase activity. Abdominal pain is the most common presenting symptom and usually persists for several days. Other clinical features include: constipation, nausea and vomiting, tachycardia, limb weakness, hypertension, urine discolouration, delirium, seizures, and depression.

Hyponatraemia, found in approximately 20% of patients with symptomatic AIP, is generally due to SIADH. Hypothalamic damage, with neuronal loss in the supraoptic and paraventricular nuclei at the level of the median eminence, has been described in patients who died of AIP complicated by SIADH. Although hyponatremia has been associated with acute porphyria, it is not a usual feature leading to the diagnosis. It is even more uncommon for nephrologists to make the diagnosis. AIP should be consider in differential diagnosis of hyponatremia associated with abdominal pain, seizures, hypertension and discolored urine

PS2-FRI-257

Quality of life in cystinosis patients

E. Elenberg*¹

¹Baylor College of Medicine, Houston, Texas, USA

Objectives: The objective was to evaluate the quality of life (QOL) in cystinosis patients and compare to their parents’ QOL perception. The hypothesis was that the perception of QOL by children would be better than their parents think.

Methods: Pediatric Quality of Life (PedsQL™) Survey was delivered via an interview. The collected answers were scored by 2 domains: Physical Health and Psychosocial Health (including: Emotional, Social and School functioning). The Total Score was calculated as the mean of the sum of all the items.

Results: PedsQL™ was answered by 28 respondents: 14 Cystinosis patients (5–18 y old) and 14 parents. Total Scores calculated from Cystinosis patients were significantly higher than those of their parents (76 vs. 62, p = 0.019). Although there was no significant difference in the Physical Health domain, the Psychosocial Health domain analysis revealed a significant difference between Cystinosis patients (higher score) and their parents (75 vs. 60, p = 0.021). The data was compared to previously published healthy and end-stage-renal disease (ESRD) subjects, using Two-sample t test with unequal variances. Comparison of Total Score to healthy subjects revealed a lower score for Cystinosis patients and their parents. For Cystinosis patients score 76 vs. healthy score 87 (p = 0.004) and their parents 62 vs. healthy score 87 (p = 0.0001). There was no statistically significant difference in total score between Cystinosis (patients and parents) versus ESRD sample.

Conclusions: Cystinosis patients perceive their QOL better than their parents think (statistical significance in Total Score and Psychosocial Health domain). Comparing Cystinosis patients to healthy subjects, it is apparent that their QOL is worse, meeting the statistical significance. Comparing Cystinosis patients to ESRD patients their QOL is similar.

PS2-FRI-258

Significance of examination of concentration of IL-1 in 24 h urine for early diagnostic of renal scarring in patients with vesicoureteric reflux

I. Zorin*¹, A. Vyalkova¹, A. Zorin¹

¹Orenburg medical academy, Orenburg, Russian Federation

The aim of the study was to determine concentration of IL-1 in urine of patients with vesicoureteric reflux (VUR) and reflux nephropathy A RN A) for early diagnostic of renal scarring. We examined 60 children with RN A and VUR. All children were comparable on a gender and age. All patients underwent ultrasound, X-ray and DMSA scan. We examined concentration of IL-1 in 24 h urine of patients by ELISA. Children were divided into 2 groups:

• I with unilateral RN A according to classification of Smellie J. et all, 1975 (n = 30);

• II with VUR without renal damage (n = 30)

We established that data of concentration of IL-1 in 24 h urine of patients with VUR without renal damage was 11,98 ± 0,24 pg/ml. Concentration of IL-1 in 24 h urine of patients with unilateral RN A was 8,53 ± 0,32 pg/ml. The ranges of concentration of IL-1 in 24 h urine of patients with VUR without renal damage were significant different with concentration of IL-1 in 24 h urine of patients with RN A (p < 0,05). So, we determined that concentration of IL-1 in 24 h urine decreased in process of renal scarring. That’s why data of concentration of IL-1 in 24 h urine can be used for early diagnostic of renal scarring in children with VUR.

PS2-FRI-265

A comparison of renal biopsy findings in children in Armenia and Switzerland

H. Nazaryan¹, G. Laube³, A. Sarkissian*¹, G. Sparta³, A. Sanamyan², A. Babloyan¹, E. Leumann³, A. Gaspert⁴

¹Arabkir Joint Medical Centre, Yerevan, Armenia, ²Department of Clinical Pathology of Yerevan State Medical University, Yerevan, Armenia, ³University Children’s Hospital, Zurich, Switzerland, ⁴Institute of Surgical Pathology, University Hospital Zurich, Switzerland

Introduction: The spectrum of renal biopsy findings varies worldwide. However, criteria for performing biopsies and biopsy evaluation are not uniform and render interpretation of data difficult. To overcome these problems we compared biopsy data of native kidneys of children in Armenia and Switzerland, based on similar biopsy policy and joint work-up.

Methods: During 1993–2010 sufficient material for biopsy was obtained in 232 patients in Yerevan (EVN; age 1–18 years (11.1 ± 4.6); 56% males) and in 204 in Zurich (ZRH, age 0.1–17.9 years (8.7 ± 4.8); 63% males). Evaluation of biopsies from Armenia was done in EVN by light microscopy (LM). If amyloidosis was excluded by Congo red stain, the material was further examined in ZRH by LM, electron microscopy (EM) and immunohisto¬chemistry (last 58 samples). Biopsies from ZRH were evaluated by LM, EM and immunofluorescence (IF).

Results: The most striking difference concerns the high frequency of amyloidosis due to familial Mediterranean fever (FMF) in Armenia (23 vs 0%) and of IgA-nephropathy/HSP in Switzerland (26 vs 7%). Certain forms of glomerulonephritis (GN) tended to more frequent in Armenia than in Zurich: Membranoproliferative GN I (6 vs 4%), Membranous GN (5 vs 2%) and SLE (7 vs 4%). In contrast, the percentage of minimal change nephrotic syndrome (MCNS; 10%) and primary FSGS (10%) was identical at both places.

Conclusions: 1) The large number of amyloid nephropathy of FMF in Armenia is alarming, 2) The far higher frequency of IgA-nephropathy in the Swiss as compared to the Armenian series was unexpected; it may partially be related to earlier referral and the availability of IF in ZRH, 3) Certain forms of primary GN and SLE were observed more often in Armenia, 4) Long-term close collaboration allowed true comparison.

PS2-FRI-267

Renal biopsy findings and outcome in children with Familial Mediterranean Fever (FMF)

A. Sarkissian*¹, M. Papazyan¹, H. Nazaryan¹, A. Sanamyan², A. Gaspert³, E. Leumann⁴

¹Arabkir Joint Medical Centre, Yerevan, Armenia, ²Department of Clinical Pathology of Yerevan State Medical University, Yerevan, Armenia, ³Institute of Surgical Pathology, University Hospital, Zurich, Switzerland, ⁴University Children’s Hospital, Zurich, Switzerland

Purpose: To evaluate patients with FMF and renal involvement. FMF constitutes a major health problem in Armenia.

Methods: During 1993–2010 we observed 72 patients (age 2–18 years, 40 males) with FMF and renal involvement. FMF was diagnosed clinically and by genetic analysis (in 69). Biopsies were evaluated in Yerevan and Zurich. 58 patients were nephrotic, 4 nephritic (2 with rapid progression) and 10 had proteinuria (± hematuria).

Results: Renal biopsy showed amyloidosis in 52 (72%) patients (group A). However, 20 (28%) had other nephropathies (B): 7 minimal changes nephrotic syndrome (MCNS), 6 acute post-infectious glomerulonephritis (APGN), 3 FSGS and 4 miscellaneous (IgA nephropathy, ANCA-GN, crescentic membrano-proliferative GN (MPGN-I) and acute tubulo-interstitial nephritis). Follow-up was 5.3 ± 3 (1–13) years. In group A 22 patients died, 8 due to cardiovascular problems (5 on dialysis), 5 in uraemia refusing dialysis and 9 for unknown reasons. Of the surviving 30 patients, 12 (2 with renal insufficiency) have improved proteinuria under colchicine, 6 remain nephrotic, 3—in renal insufficiency, 8—on hemodialysis and 1—transplanted.

Group B: One patient with MPGN-I died of ESRF. Two patients with FSGS remain proteinuric and one with IgA nephropathy has recurrent hematuria and preserved function. The remaining 16 patients had a benign course: Spontaneous remission in 6 APGN and 1 with acute tubulo-interstitial nephritis; steroid-induced remission in 7 MCNS and 1 FSGS and remission after immunosuppression in 1 ANCA-GN.

Conclusions: 1) Amyloidosis is a preventable but often fatal complication of FMF, even under RRT; 2) Other renal diseases in FMF -mostly coincidental- were more frequent than expected and carry a better prognosis; 3) FMF per se does not influence prognosis of non-amyloid nephropathies; 4) Renal biopsy is important in patients with FMF and renal involvement.

PS2-FRI-268

IgA nephropathy, study of biopsy our experience

A. Madrid*¹, M. Poblet¹, L. Vega¹, L. Soler¹, N. Toran², J.C. Ferreres^2, M. Garrido², S. Chocron¹, J. Nieto¹, M. Muñoz¹

¹Pediatric Nephrology and Transplant Department, Hospital Vall d’Hebron, Barcelona, Spain ²Anatomy pathology , Hospital Vall d’Hebron, Barcelona, Spain

IgA Nephropathy is the most common nephritis worldwide. It presents itself with variable onset and outcome.the biopsy confirms the diagnosis.(Immunoflourescence mesangial deposition of IgA)

Objectives: We review the biopsies with Diagnosis of IgA Nephropathy.

Material and method: A retrospective study and analysis the medical records of children discharged with a diagnosis by biopsy of IgA nephropathy in the last 5 years.

Results: The patient population consisted of 14 children (8 boys) mean age: 9.6 years old. The percentage of children presenting macroscopic hematuria was 5 (35%);microscopic hematuria plus proteinuria (50%), hematuria plus nephrotic syndrome 2 (15%) one of them with renal failure (Stage IV; RGF 45 ml/min/1.73 mt2). Biopsy specimens of IgA patients showed a wide variety of lesions, but the majority was de medium grade; grade II or III (mesangioproliferative, segmental mesangial cell proliferation), only one case extra capillary proliferative (crescent in 14%. Glomeruli).

Treatment: No treatment (3 pat.); Oil Fish (7 pat.) Immunoglobulin intravenous (2); Steroids (5 Pat.) ; ARB (angiotensin receptor blocker) or ACE (angiotensin-converting enzyme inhibitors) (5 pat.) After a mean 24.6 months of follow-up, no patient had renal insufficiency.

Conclusion: No treatment in spontaneous remission. Treatment with oral corticosteroids is widely used therapy with moderately severe IgAN. Our patients with severe disease were treated with corticosteroids and immunoglobulin. The use of an ACE or as ARB initially was therapy for patient with proteinuria. Our study confirmed that IgA Nephropathy is generally a benign disease in children. But microscopic hematuria continued and is present in 35% and recurrence in 50%

PS2-FRI-272

A phase II study of eculizumab in adolescent/adult patients with atypical hemolytic uremic syndrome (aHUS) receiving chronic plasma exchange/infusion: interim efficacy and safety analysis

Christoph Licht*¹, Petra Muus², Christophe Legendre³, Kenneth Douglas⁴, Maryvonne Hourmant⁵, Yahsou Delmas⁶, Maria Herthelius⁷, Antonella Trivelli⁸, Timothy Goodship⁹, Camille Bedrosian¹⁰, Chantal Loirat¹¹

¹The Hospital for Sick Children, Toronto, ON, Canada, ²Radboud University Nijmegen Medical Centre, Netherlands, ³Hôpital Necker, Paris, France, ⁴Beatson West Scotland Cancer Centre, United Kingdom, ⁵CHU Nantes-Hotel Dieu, France, ⁶CHU Bordeaux—Pellegrin, France, ⁷Karolinska University Hospital, Sweden, ⁸Istituto G Gaslini, Italy, ⁹Newcastle University, Newcastle, United Kingdom, ¹⁰Alexion Pharmaceuticals Inc, Cheshire, USA, ¹¹Hôpital Robert Debré, France

Objectives: aHUS is a rare, life-threatening disease caused by chronic uncontrolled complement activation, which leads to systemic thrombotic microangiopathy (TMA). Sixty percent of patients will have ESRD/death within the first year of diagnosis, despite chronic plasma exchange/infusion. We investigated the efficacy/safety of eculizumab, a terminal complement inhibitor, in adolescent/adult patients with aHUS receiving chronic plasma exchange/infusion.

Methods: Phase II, controlled, open-label, single-arm study. After completing an 8-week observation period, patients ≥12 years with aHUS discontinued plasma exchange/infusion and began 26 weeks of eculizumab treatment (900 mg/week for 4 weeks, 1200 mg at Week 5, then 1200 mg q2 weeks). All patients received a meningococcal vaccine ≥2 weeks before starting eculizumab. The primary endpoint was TMA event-free status (≥12 consecutive weeks of stable platelet count; no plasma exchange/infusion; no new dialysis). Secondary endpoints included TMA intervention rate (number of plasma and new dialysis events/patient/day), renal function and safety.

Results: In this interim analysis, 20 patients received eculizumab, of whom 15 had ≥12 weeks of follow-up. Median age was 28 years (range: 13–63), 70% had an identified complement regulatory factor mutation(s) (CRFM), 40% had a kidney transplant, 55% had eGFR levels <30 ml/min/1.73 m², 10% were on dialysis, and 45% were receiving 2–3 plasma exchange/infusion sessions/week at baseline. For the primary endpoint, 13/15 (87%) patients (95% CI: 60%–98%) achieved TMA event-free status with eculizumab. Median TMA intervention rate decreased significantly from 0.16 to 0 events/patient/day (p < 0.0001). eGFR stabilized/increased with eculizumab compared with the observation period (median 31 vs. 27 ml/min/1.73 m²). Eculizumab was effective for all secondary endpoints, regardless of the presence of identified CRFM. The most common adverse events were diarrhea, headache, hypertension and nausea (mild–moderate).

Conclusions: Eculizumab significantly sustained suppression of TMA, led to permanent discontinuation of chronic plasma exchange/infusion, maintained renal function, and was well tolerated in patients with aHUS.

PS2-FRI-273

Eculizumab in adolescents/adult patients with atypical hemolytic uremic syndrome resistant to plasma exchange/infusion: a phase II efficacy and safety study

Chantal Loirat* ¹, Sunil Babu², Richard Furman³, Neil Sheerin⁴, David Cohen⁵, Osama Gaber⁶, Frank Eitner⁷, Yahsou Delmas⁸, Larry Greenbaum⁹, Camille L. Bedrosian¹⁰, Lothar Bernd Zimmerhackl¹¹ Christophe Legendre¹²

¹Hôpital Robert Debré, France, ²Fort Wayne Med, IN, USA, ³Weill Cornell Med College, NY, USA, ⁴Newcastle University, Newcastle upon Tyne, UK, ⁵Columbia Univ Med Center, NY, USA, ⁶Methodist Hospital, TX, USA, ⁷University Aachen, Aachen, Germany, ⁸CHU Pellegrin Bordeaux, France, ⁹Emory University, GA, USA, ¹⁰Alexion Pharmaceuticals Inc., Cheshire, USA ¹¹University Innsbruck, Austria, ¹²Universite Paris Descartes & Hôpital Necker, France

Objectives: aHUS is a rare, life-threatening disease caused by chronic, uncontrolled complement activation, which leads to systemic thrombotic microangiopathy (TMA). Within the first year of diagnosis, despite plasma exchange/infusion (PE/PI), ∼60% of patients will have ESRD/death. We investigated the efficacy/safety of eculizumab, a terminal complement inhibitor, in patients with PE/PI-resistant aHUS.

Methods: Phase II, controlled, open-label, single-arm 26-week study. Patients ≥12 years with PE/PI-resistant aHUS (persistent TMA despite ≥4 PE/PI sessions 1 week before screening) started eculizumab (900 mg/week for 4 weeks, 1200 mg in Week 5, then 1200 mg q2 weeks). All patients received a meningococcal vaccine. Primary endpoint was change in platelet count. Secondary endpoints included TMA event-free status (≥12 weeks of stable platelet count, no PE/PI, no new dialysis), TMA intervention rate (plasma and new dialysis events/patient/day), renal function, and safety.

Results: Fifteen of 17 enrolled patients (median age = 28 years [17–68 years]) received eculizumab for 26 weeks. At baseline, 76% had an identified complement regulatory factor mutation (CRFM), 41% had a kidney transplant, and 29% were on dialysis. Platelet count increased by a point estimate 73 × 10⁹/L (95%CI:40–105 × 10⁹/L) from baseline to Week 26 (p = 0.0001), and was seen as early as Day 7 and maintained thereafter. Eculizumab treatment normalized platelet count in 13/15 (87%) patients with abnormal baseline values. Fifteen (88%) patients became TMA event-free. Median TMA intervention rate decreased significantly from 0.88 to 0 events/patient/day (p < 0.0001). In 9/17 (53%) patients eGFR improved by >15 ml/min/1.73 m². In 10 (59%) patients CKD improved by ≥1 stage. Importantly, 4/5 patients became dialysis-free. All efficacy endpoints were similar for patients with/without a CRFM. The most common adverse events were headache, anemia and diarrhea.

Conclusions: Eculizumab demonstrated significant improvements in platelet count and TMA, removing the need for PE/PI. Eculizumab restored renal function, rescued nearly all patients from dialysis and was well tolerated.

PS2-FRI-275

Succinate activates the collecting duct renin-angiotensin system

A. Prokai* ^1,2, J. Burford¹, H. Gevorgyan¹, Z. Peterfi¹, S. L. Vargas¹, J. Peti-Peterdi¹

¹Department of Physiology and Biophysics and Department of Medicine, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California, USA, ²1st Department of Pediatrics, Semmelweis University, Budapest, Hungary

Objectives and study: The novel metabolic receptor GPR91 controls renin release, the rate-limiting step of RAS. Furthermore, the renal collecting duct (CD) is the major source of (pro)renin in diabetes. Since the highest GPR91 expression was found in the CD, this study investigated whether succinate, the ligand of GPR91 regulates the local CD RAS.

Methods and results: Western blot analysis of succinate-treated M1 cells (CD cell line) showed a dose-dependent, 2–2.5-fold elevation in pERK½, pp38, COX2, renin, prorenin and its receptor [(P)RR]. In WT and GPR91−/− control and STZ-diabetic (DM) mice, CD pERK1/2 (by immunofluorescence) and urinary PGE2 excretion (measured by ELISA) increased 4–20 fold in DM mice and were GPR91-dependent. Medullary (pro)renin and (P)RR protein expression (by immunoblotting) and renin activity in the CD tubular fluid (visualized in vivo using multiphoton microscopy and a fluorogenic renin substrate delivered by renal micropuncture) increased 4–5 fold in WT DM vs. control mice, which was completely abolished in GPR91−/− DM mice.

Conclusions: This is the first, direct demonstration of CD renin activity in vivo. Succinate accumulation and GPR91 signaling are novel (patho)physiological regulatory mechanisms that activate the local RAS in the CD via MAP kinases and COX2, PGE2 release, and increased (pro)renin and (P)RR synthesis. Succinate and GPR91 may be important regulators of the local CD RAS in DM and may serve as new therapeutic targets in diabetic nephropathy.

Supported by grants from NIH DK064324; AHA EIA 0640056N; Council on International Educational Exchange (CIEE) and REG_KM_09-1-2009-0016 BAROSS.

PS2-FRI-276

Changing pattern of stone composition in child with cystinuria

A. Mazo* ¹, A. Akopyan¹, S. Zorkin¹, R. Zacalucin², A. Tsygin¹

¹Scientific Center of Children’s Health RAMS, Moscow, Russian Federation, ²Shubnikiv Institut of crystallograhy Russian Academy of Sciences, Moscow, Russian Federation

Objectives and study: Cystinuria accounts 1–5% of urolithiasis in children. Mutations of transporters in proximal renal tubes lead to increasing concentration of diabasic amino acids in the urine. Only cystine is poorly soluble, especially at low urine pH, and could form stones.

Methods: We examined 58 children with urolithiasis and found 3 patients (5%) with cystine stones. We performed chemical analysis of urine and X-ray-diffraction analysis of the stones.

Results: One child had unilateral kidney stone from 3,5 months and bilateral—from 6 months. We examined this child at 7 months old. Qualitative urine analyses of cystine was slightly-positive (+). Urinary excretion of calcium, oxalate, uric acid, fhosphate, magnesium was normal. Extracorporal lithotripsy was done at 7 month and all fragments went away. Stone consisted of L-cystine 95% and whewellite with weddellite-5%. We diagnosed cystinuria and gave recommendations (high-fluid intake, low-sodium diet, excluding eggs, fish, poultry, cheese, maintenance pH urine level >7,4). After 5 months new stone 7 mm was revealed. Urine analysis of cystine was negative. Urinary excretion of calcium, oxalate, uric acid, fhosphate was normal. Magnesium urinary excretion was low. Extracorporal lithotripsy was done at 13 month and all fragments went away. Stone consisted of whewellite 33%, weddellite 65%, L-cystine 2%. Child got new recommendation (high-fluid intake, low-sodium diet, excluding oxalate-rich food, maintenance pH urine level 6,2–6,8, magnesium suplement) and during 1 year he remained free from stones.

Conclusions: We speculate that in some cases cystine stone formation can be due to transient neonatal cystinuria. However, despite the elimination of the etiological factor these children should be included in a risk group for urolithiasis.

PS2-FRI-277

Metabolic features in Russian children with urolithiasis

A. Mazo* ¹, A. Akopyan¹, S. Zorkin¹, H. Vasiljeva¹, N. Mayanskiy¹, R. Zacalucin², A. Tsygin¹

¹Scientific Center of Children’s Health RAMS, Moscow, Russian Federation, ²Shubnikiv Institut of crystallograhy Russian Academy of Sciences, Moscow, Russian Federation

Objectives and study: Metabolic abnormalities account for about 25–90% of cases in pediatric urolithiasis. Correspondence between urine analyses and stone compositions in russian children hasn’t been investigated.

Methods: We examined 58 children with urolithiasis (88% with kidney stones, 9% with ureter stones, 3% with combined kidney and bludder stones). We performed chemical analysis of urine samples and X-ray-diffraction analysis of 42 stones.

Results: Calcium oxalate was the predominant constituent in 62% of the kidney stones, followed by calcium phosphate (19%), cystine (7%), dyhidrate urine acid (7%), uric acid (2.5%) and struvite (2.5%). Etiology was obviously metabolic in 12% and possibly metabolic in 33%. 10% were secondary to obstruction etiology but not to infection. Etiology in 24% remained unknown. Stone composition and metabolic disorders are similar to that in central Europe and North America. It\’s important that in some cases urinary excretion of lithogenic substances didn\’t reflect stone composition. Three patients with oxalate stones had hyperphosphaturia, one patient with phosphate stone had hypercalciuria and one patient with struvite had also hypercalciuria. In some cases (7%) we couldn\’t reveal any risk factors (exception heredity) but stones grew up after EUWL. In one case there wasn\’t any risk factors but stone re-appeared after full removal.

Conclusions: In many cases stone forming doesn\’t depend on known metabolic features. Careful attention is necessary to children with unrecognized causes of urolithiasis, especially with recurrent stones, and to children with contradictory urine and stone analyses.

PS2-FRI-278

Prevalence of R229Q polymorphysm of NPHS2 gene in Russian children with steroid-resistant nephrotic syndrome

A. Tsygin* ¹, V. Kornienko², T. Vashurina¹, O. Zrobok¹, M. Matveeva¹, Lj. Leonova³, K. Baranov¹, V. Pinelis²

¹Nephrology, NCZD Centre for Children’s Health, Moscow, Russian Federation, ²Genetics, NCZD Centre for Children’s Health, Moscow, Russian Federation, ³Pathology, NCZD Centre for Children’s Health, Moscow, Russian Federation

Objectives and study: Metabolic abnormalities account for about 25–90% of cases in pediatric Mutations of NPHS2 gene resulting in podocin synthesis dysregulation account a significant proportion in patients with idiopathic steroid resistant nephrotic syndrome (SRNS) worldwide. In order to investigate the prevalence of these mutations in Russian children with SRNS we performed a direct sequencing of NPHS2 gene in 59 children with SRNS and MCD/FSGS renal pathology, 15 children with steroid-sensitive NS and 15 healthy subjects.

Apparently, among known mutations a most frequent was R229Q, which is considered to be a non-silent polymorphism potentially causing SRNS. It was found in a heterozygous state in 11 (19%) of 59 SRNS patients. All except one of them had a non-compound heterozygous mutation. However, in six of that patients R229Q was accompanied with A318A or C228T, a so called silent polymorphism not affecting normally a protein synthesis. A unique finding was that among that 11 patients one had Schimke syndrome with a progressive course.

Heterozygous R229Q polymorphism was detected also in 2 of 15 healthy subjects and in one of 15 steroid-sensitive patients associated with A318A in one from each group.

Other mutations in SRNS group were homozygous E87X in two brothers from the same family, compound heterozygous R138Q and E87X, R138Q and V165X.

We conclude that at least 25% of idiopathic SRNS may be caused by HPHS2 gene mutations in Russian population. The most frequent mutation/polymorphism is R229Q and it’s more likely to cause a disease being associated with “silent” polymorphisms. A hot spot analysis for R229Q may be a useful tool to apply in steroid resistance.

PS2-FRI-284

Etiology of nephrocalcinosis in Albanian children

D. Shtiza* ¹, R. Xhepa¹, O. Xhango¹, S. Lito², F. Cenko³

¹Department of Pediatrics, Service of Nephrology, University Hospital Centre of Tirana, Albania, ²Medical University of Sofia, Bulgaria , ³Public Health Specialist, Faculty of Medicine, Tirana University, Albania

Objectives: This retrospective study analyzes the etiology of nephrocalcinosis (NC) in Albanian children. We evaluated presenting complaints, clinical manifestations, growth and development and renal function at presentation; correlation of growth and renal function to changes in nephrocalcinosis.

Methods: Twenty five children (18 boys), followed with the diagnosis of NC, from 2001–2010 in the nephrology unit of our hospital were included in the study. The median age at diagnosis was 23 (1–120) months. The median period of follow-up was 39 (1–118) months. The patients’ height, weight and corresponding standard deviation scores (SDS) of WHO were recorded.

Results: The etiology of NC included distal renal tubular acidosis in 36% patients, vitamin D excess in16% of patients, idiopathic hypercalciuria and hyperoxaluria in 8% each. Other causes were Bartter syndrome, Fanconi syndrome, Dent disease and X-linked hypophosphataemic rickets. No cause for NC was found in 16% of patients. Presenting symptoms were failure to thrive in the first year of life (62%), urinary tract infection, vomiting and anorexia, bladder voiding dysfunction or psychomotor delay (15%). In 28% of cases NC was detected incidentally. Glomerular filtration rate (GFR) were ameliorated from 74,24 (27–121) ml/min/1.73 m² at diagnosis to 96,83 (67–130) ml/min/1.73 m² (P < 0.001). During a follow-up growth standard score improved from a median of −1,87 (−4,75 ÷ +2,0) to −1,1 (−4,09÷ +2,0) for height (P = 0,01) and from −1,77 (−4,19÷ +2,0) to −0,53 (−4,00÷ +3,00) for weight (p = 0,01).

Conclusion: The most frequent causes of NC were distal renal tubular acidosis and vitamin D intoxication in childhood in Albania. We were able to find the cause of NC in majority of children. Our results show that the treatment of the underlying conditions is associated with catch-up growth and amelioration of glomerular filtration rate in many children, but not with reduction in the degree of NC in the majority of cases.

PS2-FRI-285

Shiga-like toxin upregulates production of C3 mRNA and protein in human endothelial cells

E. Volokhina* ¹, A. Vos1, T. van der Velden¹, D. Westra1, N. van de Kar¹, L. van den Heuvel^1,2

¹Radboud University Nijmegen Medical Centre (RUNMC), The Netherlands, ²University Hospital Leuven, Belgium

Objectives and study: Most of the HUS cases are preceded by infection with Shiga-like toxin (Stx) producing Escherichia coli (STEC). Although Stx inhibits protein synthesis, the exact mechanism of how Stx exposure leads to HUS is poorly understood. Complement dysregulation is a hallmark of less common non-STEC HUS. Therefore, we studied whether Stx1 is able to alter complement gene expression in human endothelial cells.

Methods: HUVEC from 9 donors and conditionally immortalized and primary human glomerular microvascular endothelial cells (GMVEC) were treated for 24 hours with Stx1 with or without prestimulation with TNFα or LPS. The mRNA levels were analyzed by qPCR and protein levels were measured using ELISA. Protein synthesis inhibition was assessed by testing 3H-leucine incorporation.

Results: C3 mRNA levels in HUVEC and GMVEC were elevated 3 ± 1 and 6 ± 1 fold, respectively, after Stx1 treatment. This effect was greatly enhanced by prestimulation with TNFα or LPS to 45 ± 14 and 1698 ± 672 fold. C3 protein levels were upregulated up to 6 fold and 8 fold for prestimulated HUVEC and GMVEC. Protein synthesis inhibition only partially explains the difference between C3 mRNA and protein levels. No major impact was observed on CFI, CFH and MCP mRNA expression.

Conclusions: Our results suggest that exposure of HUVEC and GMVEC cells to Stx1 leads to an increased production of C3, especially on the mRNA level, and marginally changed levels of CFI, CFH and MCP complement inhibitors, that might lead to local inefficient inactivation of C3b and damage of glomerular endothelial cells in STEC-HUS through improper complement activation.

PS2-FRI-286

Novel DNA alterations in FCN1 and FCN2 genes in atypical HUS patients

E. Volokhina* ¹, D. Westra¹, A. Spoelstra¹, N. van de Kar¹, L. van den Heuvel^1,2

¹Radboud University Nijmegen Medical Centre (RUNMC), The Netherlands, ²University Hospital Leuven, Leuven, Belgium

Objectives and study: Atypical hemolytic uremic syndrome (aHUS) results from defective complement control on the cell surface and is associated with mutations affecting alternative complement pathway, clusterin, thrombomodulin and with autoantibodies to Factor H. The aHUS etiology is of prognostic value for the patient, particularly for renal transplantation. Nevertheless, in 50% of cases genetic cause is not found. Lectin complement pathway activation is associated with glomerular damage in IgA nephropathy. In this study we screened the aHUS patient cohort for sequence variations in genes encoding ficolins (pattern recognition molecules) of the lectin pathway to explore whether this pathway might be involved in complement damage to the glomeruli in aHUS.

Methods: The FCN1, FCN2 and FCN3 genes were analyzed by means of PCR and DNA sequencing using genomic DNA of 56 aHUS patients and of 141 healthy controls. Impact of the found missense sequence variations on the protein function was analyzed using prediction software and available structural data.

Results: One and three sequence variations were found in FCN1 and FCN2, respectively, in four different aHUS patients. These variations resulted in amino acid substitutions. None of these changes were present in dbSNP, described before, or found by us in a group of 141 control individuals. No alterations were found in the FCN3 gene. The observed sequence variations are predicted to affect protein function.

Conclusions: Novel aHUS predisposing alterations in FCN1 and FCN2 are described. Our results suggest that the lectin pathway might be involved in the pathogenesis of aHUS.

PS2-FRI-288

Eculizumab therapy for atypical hemolytic uremic syndrome (aHUS) in pediatric patients: efficacy and safety outcomes from a retrospective study

G. D. Simonetti* ¹, R. A. Gruppo², N. Rodig³, J. Hernandez⁴, A. L. Lapeyraque⁵, J. Sherwinter⁶, O. Fremont⁷, C. B. Langman⁸, V. Baudouin⁹

¹Bern University Children’s Hospital, Inselspital, Bern, Switzerland, ²Cincinnati Children’s Hospital Medical Center, Cincinnati, United States, ³Children’s Hospital Boston, Boston, United States, ⁴Sacred Heart Children’s Hospital, Spokane, United States, ⁵CHU Sainte-Justine, Montréal, Canada, ⁶Children’s Healthcare of Atlanta, Atlanta, United States, ⁷Maine Medical Center, Portland, United States, ⁸Children’s Memorial Hospital, Chicago, United States, ⁹Hôpital Robert Debré, Paris, France

Objective: aHUS is a rare, life-threatening disease in which chronic, uncontrolled terminal complement activation leads to systemic thrombotic microangiopathy (TMA) that ultimately causes multi-organ damage/failure and death. In prospective clinical trials of adult/adolescent aHUS patients, the complement C5-inhibitor eculizumab controlled the TMA process, prevented and/or reversed kidney damage and reduced chronic plasma exchange/infusion (PE/PI) requirements. Our objective was to assess the efficacy/safety of eculizumab therapy for aHUS in pediatric patients outside of clinical trials.

Methods: A retrospective data collection analysis of 30 aHUS patients receiving >=1 eculizumab dose outside of clinical trials from 2007–2009 was conducted. Outcomes for patients aged <12 y are presented herein.

Results: Fifteen patients were evaluated (aged <2 y[n = 5]; 2–4 y[n = 3]; 5–11 y[n = 7]). At baseline, 47% of patients had platelet counts <150 × 109/L, 20% had eGFR levels <30 mL/min/1.73 m², 67% had elevated serum-LDH levels, and 47% had an identified complement regulatory factor mutation. Baseline biological parameters were normal for one patient receiving eculizumab to prevent TMA in a kidney graft. During eculizumab therapy, 93% of patients achieved or maintained platelet normalization (>15 × 109/L), 53% demonstrated hemoglobin improvement >=20 g/L, and 53% demonstrated eGFR improvement >=15 mL/min/1.73 m². Most patients (80%) attained TMA event-free status (platelet normalization, no PE/PI or dialysis) during eculizumab therapy, while 7/14 (50%) of patients with >=1 abnormal biological parameter at baseline achieved complete TMA response (platelet/LDH normalization plus ≥25% serum creatinine reduction). Further, mean TMA intervention rate (PE/PI or dialysis events/patient/day) was significantly reduced from 0.67 pretreatment to 0.01 with eculizumab treatment (P < 0.0001). Eculizumab efficacy was similar across age groups and was well tolerated.

Conclusions: These results, consistent with those from adult/adolescent trials, show that eculizumab treatment is well tolerated and can control TMA, reduce need for PE/PI and improve kidney function, thereby demonstrating the promising potential of eculizumab as a new standard of care for aHUS.

PS2-FRI-290

Quantitative assessment of glomerular tuft changes in nephrotic syndrome in children

I. Sakharau* ¹, E. Cherstvy¹, A. Sukalo¹, T. Letkovskaya¹, V. Savosh¹, N. Tur²

¹Belarusian State Medical University, Minsk, Belarus, ²Republic Center for Children Nephrology and Renal Replacement Therapy, Minsk, Belarus

Objectives: To study quantitative changes of cells and capillaries in kidney glomeruli of children with primary nephrotic syndrome (PNS).

Methods: Kidney biopsy specimens were obtained from 31 children with PNS and 30 children with isolated hematuria (control group). Clinical and laboratory data were collected. Paraffin-embedded, formalin-fixed sections were stained with WT1 antibody. Images of five glomeruli from each section were taken and analyzed using ImageJ software. Glomerular tuft area was measured by drawing a region of interest around the tuft. The number of WT1-positive nuclei (podocytes) was counted, as well as the number of other cells (WT1-negative - mesangial and endothelial) and that of capillary lumens. The following indices were calculated: mean tuft area of five glomeruli, podocyte density (podocyte number per 10000 sq mkm), other cells density (other cells number per 10000 sq mkm), podocyte number per capillary, and capillary density (capillary number per 10000 sq mkm).

Results: Of the 33 children with PNS, 22 children had minimal changes (MC) at histology, 4 children had mesangial proliferation (MP), 5 children had focal segmental glomerular sclerosis (FSGS). In hematuria group—4, 23 and 3 respectively. There were no significant differences in mean tuft area and in podocyte number per capillary between the two groups. Podocyte density was significantly decreased in NS group (23,63 ± 8,11) compared with hematuria group (33,24 ± 8,43) (p < 0,001). Podocyte density was also decreased in each of histological variants. Other cells density had no significant differences. Podocyte density and capillary density in NS group decreased in direction MC > MP > FSGS showing positive correlation (rho = 0,52, p = 0,003). In hematuria group, no differences in morphometric indices between histological variants were found.

Conclusions: The number of podocytes and capillaries in kidney glomeruli is decreased in children with primary NS.

PS2-FRI-291

Kidney electron microscopy in children: first steps in Belarus

I. Sakharau* ¹, E. Cherstvy¹, A. Sukalo¹, T. Letkovskaya¹, V. Savosh¹, N. Tur²

¹Belarusian State Medical University, Minsk, Belarus, ²Republic Center for Children Nephrology and Renal Replacement Therapy, Minsk, Belarus

Objectives: Electron microscopy (EM) has been used for the morphological diagnosis of glomerular diseases for about forty years. Some researchers have observed that about 85% of renal biopsies had an indication of EM for diagnostic confirmation and in 25% of cases EM is essential for diagnosis. Until recently kidney electron microscopy was not performed routinely in Belarus. The objective of this study is to characterize the ultrastructure changes of kidney seen by EM.

Methods: 70 kidney biopsies in children were performed in 2010 in Republic Center for Children Nephrology and Renal Replacement Therapy (Minsk). Specimens for EM were obtained from 24 of them. Ultrathin sections were stained with uranyl acetate and lead citrate, and examined with a JEM-1011 (Jeol, Japan) transmission electron microscope.

Results: Effacement of podocyte foot processes, either diffuse or focal, was observed in all cases of nephrotic syndrome (17 children), as well as microvillous transformation of podocyte body. Endothelial hypertrophy was also noted. Podocyte vacuolization was seen in cases of heavy proteinuria. Focal segmental glomerular sclerosis (FSGS) was diagnosed by light microscopy in three cases of frequently relapsing nephrotic syndrome; podocyte detachment and glomerular basal membrane (GBM) denudation were seen by EM, as well as intramembranous electron dense deposits. Splitting of GBM and intramembranous electron dense deposits were noted in one case of hematuria and nephrotic range proteinuria (membranoproliferative glomerulonephritis). One patient had subtotal GBM thinning (Alport syndrome).

Conclusions: EM was principally contributory for diagnosis. Minimal change disease was diagnosed by foot processes effacement. In cases of FSGS and membranoproliferative glomerulonephritis light microscopy changes were supplemented with characteristic EM changes. In case of Alport syndrome EM was diagnostic by demonstrating GBM thinning.

PS2-FRI-295

Characteristics and outcome of children with primary hyperoxaluria requiring renal replacement therapy: an ESPN/ERA-EDTA study

J. Harambat* ¹, K .J. van Stralen¹, L. Espinosa², J. W. Groothoff¹, S. A. Hulton³, A. Jankauskiene⁴, E. Verrina⁵, F. Schaefer⁶, K. J. Jager¹, P. Cochat⁷

¹Academic Medical Center, Amsterdam, the Netherlands, ²La Paz Children’s Hospital, Madrid, Spain, ³Children’s Hospital NHS Trust, Birmingham, UK, ⁴University Children’s Hospital, Vilnius, Lithuania, ⁵Gaslini Children’s Hospital, Genoa, Italy, ⁶University Children’s Hospital, Heidelberg, Germany, ⁷University Children’s Hospital, Lyon, France

Objectives: Data on management and outcome of ESRD in children with primary hyperoxaluria (PH) is scarce. We aim to describe the characteristics, treatment and outcome in children starting renal replacement therapy (RRT) for ESRD due to PH.

Methods: This study included pediatric patients (<19 years) who started RRT between 1979 and 2009 from 31 European countries providing data to the ERA-EDTA and the ESPN/ERA-EDTA Registries. Kaplan-Meier and Cox regression analyses were performed to examine patient survival on RRT as well as first kidney graft survival for PH and non-PH patients.

Results: Of the 9247 incident pediatric patients on RRT, 100 (1.1%) had PH. PH children were significantly younger than non-PH children at the start of RRT (median 5.3 vs. 11.4 years). Median age at RRT of PH children decreased significantly over time from 9.8 in 1979–1989 to 4.6 in 1990–1999 and 1.5 years in 2000–2009. Among PH patients, survival was 86, 79, and 76% at 1, 3 and 5 years since start of RRT, compared to 97, 94, and 92% in non-PH patients. Adjusted for age, sex and era, PH children had almost a 3-fold higher risk of death within 5 years after start of RRT compared to non-PH patients (HR 2.70; 95%CI 1.73–4.23). Sixty-four PH children received a first kidney or liver-kidney transplant after a median time on dialysis of 14 months (interquartile 7–23). There were 22 kidney graft losses (defined as return to dialysis or death) during follow-up. Kidney graft survival was 67, 63 and 54% at 6 months, 1 and 3 years post-transplantation.

Conclusions: The occurrence of ESRD in children with PH raises specific issues because of the difficult management and the disease severity in infants. Outcome of RRT for PH remains poor in this age group.

PS2-FRI-298

Improvement in the renal prognosis in nephropathic cystinosis: data from the ESPN/ERA-EDTA registry

K. J. van Stralen* ¹, F. Emma², K. J. Jager¹, E. Verrina³, F. Schaefer⁴, G. F. Laube⁵, M. Lewis⁶, E. Levtchenko⁷

¹ESPN/ERA-EDTA Registry, Academic Medical Center, The Netherlands, ²Bambino Gesú Hospital, Italy, ³Gaslini Children\’s Hospital, Genoa, Italy, ⁴University of Heidelberg Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany, ⁵University Childrens Hospital, Zurich, Switzerland, ⁶Royal Manchester Children’s Hospital, Manchester, United Kingdom, ⁷University Hospitals Leuven, Leuven, Belgium

Objectives and study: Nephropathic cystinosis (NC) is a rare autosomal recessive disorder of lysosomal cystine transporter cystinosin, occurring in 1–2 per 100,000 newborns. Because of the rarity of the disorder, long-term outcome data in NC patients are scarce.

Methods: Within the framework of the ESPN/ERA-EDTA Registry, information was available on a total of 245 NC patients from 18 countries. NC patients were matched to comparable children on renal replacement therapy (RRT). Survival analysis was performed using Kaplan Meyer analyses. Other analyses were performed using logistic regression, and linear and logistic mixed model analyses.

Results: Between 1979 and 2008 mean age at start of RRT among NC children strongly increased from 8.8 years to 12.7 years, while this was not seen in other children on RRT. Five-year survival after start of RRT improved in NC patients from 86.1% in 1990 to 100% in 2000. As compared to other pediatric RRT patients from the same country, gender and age, NC patients more often received a renal allograft, both pre-emptively (OR 2.1, 95%CI 1.3–3.6 as compared to peritoneal dialysis) and in total during follow-up (RR 1.09, 95%CI 1.00–1.17).

NC patients on dialysis were less hypertensive than their peers matched on age, country, and dialysis modality, and had lower, close to normal PTH levels. Whilst they slightly improved their height at start of RRT during the past decade, they were still significantly shorter at the start of RRT than other children. No differences were found in albumin, hemoglobin and phosphate levels between NC patients and their peers on RRT.

Conclusions: We demonstrated improved survival of the renal function before the initiation of RRT as well as patient survival after the start of RRT in European NC patients over the last two decades. Short stature remains a severe complication of NC.

PS2-FRI-303

DNA sequence variants of NPHS2 gene in 674 children with SRNS

A.Berdeli*¹, S. Mir², S. Nalbantoglu¹, M. Atan¹, D.Tigli¹, N.Dincel²

¹Ege University School of Medicine Children’s Hospital Molecular Medicine Laboratory, Izmir, Turkey, ²Ege University School of Medicine Children’s Hospital Department of Pediatric Nephrology, Izmir, Turkey

Objectives and study: Nephrotic syndrome is characterized by podocyte abnormalities. The aim of the present study is to perform podocin gene mutation analysis and associate the obtained results with the clinical phenotype of large scale SRNS patients.

Methods: 674 clinically diagnosed SRNS patients and 100 healthy control group who do not have any symptom or positive familial history were enrolled in this study. After genomic DNA extraction, molecular analysis involved Polymerase Chain Reaction (PCR) and DNA Sequencing Analysis. Bidirectional DNA cycle sequencing analysis of all coding exons and adjacent intronic segments of NPHS2 gene was performed and analyzed at ABI3130xl Genetic Analyzer. For the NPHS2 gene mutation (−) patients, mutation analyses of other podocyte genes involving NPHS1, WT1, TRPC6, CD2AP, and ACTN4 were also investigated.

Results: 674 clinically diagnosed SRNS patients comprised of 66 familial and 608 sporadic cases. A total of 47 different mutations were determined in the NPHS2 gene, and 32 of which were characterized as a novel mutation. Mutation positive rate of the total group was 20% and mutation positive rate of sporadic group was 19.2%. In the familial group, mutation positive rate was 31%. In the mutation positive NPHS2 group, most of the mutations were found out to harbor in exons 1, 4, and 5 while no mutation was found in exon 6 of the respective gene. SNPs combined with mutations involved G34G, A138A, H21H, L346L, S96S, and L344L from exons 1 to 8. G34G and A138A were also found in the normal population as a normal variant. Among the sequence variations, homozygosity was determined lower than heterozygosity (1:3).

Conclusions: Genetic diagnosis has great importance in paralel to clinical diagnosis in particular for the early diagnosis, follow-up of the clinical course, and therapy in SRNS patients.

PS2-FRI-305

Keeping an eye on the kidney (TINU syndrome)

J.Vara*¹, R.Muley¹, C.Diz-Lois¹

¹Hospital Univesitario 12 Octubre, Madrid, Spain

Objectives and study: To recognize the association between acute tubulointerstitial nephritis and uveitis (TINU syndrome), a rare disease with both renal and ophthalmologic involvement.

Patients and methods: We report a previously healthy 15 year old boy diagnosed of bilateral anterior uveitis 4 months before, and treated topically with steroids and cycloplegics and oral prednisone (40 mg/day) for 10 days. Ophthalmologic symptoms resolved with no relapses. He was referred to Nephrology because of casual high serum creatinine levels. The physical examination and blood pressure were normal. Laboratory studies showed normal haemoglobin and erythrocyte sedimentation rate, serum creatinine 1,78 mg/dl, glomerular filtration: 63 ml/min/1.73 m² and hypophosphatemia. Urinalysis showed tubular dysfunction: glycosuria, aminoaciduria, phosphaturia and elevated urinary beta2-microglobulin levels. Complement fractions C3 y C4, thorax R-ray, renal ultrasounds and serological test for autoimmune or infectious diseases were normal. Renal biopsy showed a lymphocytic interstitial infiltrate involving 5% of renal tissue with inmmunohistochemical positivity to CD3-T-cell. He was diagnosed of TINU syndrome and treated with steroid therapy at a dose of 80 mg/day for 4 weeks, and slowly tapered. At a follow up of 8 months the renal function showed improvement with normal glomerular rate filtration, but persistent tubular dysfunction. He receives treatment, so far.

Results: TINU syndrome must be part of differential diagnosis of every patient with tubulointerstitial nephritis and uveitis. Clinically, uveitis is usually anterior (80%) and bilateral (77%) and occurs before renal disease in 20% of cases. Renal prognosis is considered to be good, including spontaneous recoveries, but some patients need treatment with steroids for long periods.

Conclusion: The diagnosis of TINU syndrome includes uveitis, laboratory and renal biopsy data of tubulointerstitial nephritis. Most patients have a good prognosis, but some of them may need long term therapy, including observation for many years.

PS2-FRI-306

Results of MEFV gene full DNA sequencing analysis and genetic heterogeneity in 3430 Turkish FMF patients

A.Berdeli*¹, S.Nalbantoglu¹, D.Tigli¹, M.Atan¹, I.Demirel¹, P.Mir1, S.Toparlak²

¹Ege University School of Medicine Children’s Hospital Molecular Medicine Laboratory, Izmir, Turkey, ²Ege University School of Medicine Children’s Hospital Department of Pediatric Nephrology, Izmir, Turkey

Objectives and study: This study presents familial Mediterranean fever which is a hereditary autosomal recessive autoinflammatory disorder. Here, we aimed to indicate the results of full causal gene sequencing of MEFV gene and pathogenicity of novel/rare mutations according to clinical implications.

Methods: 3430 Turkish patients clinically diagnosed with FMF and 250 healthy controls were enrolled in this study. Upon DNA extraction from blood samples of controls and patients, PCR and bidirectional DNA sequencing assays were performed.

Results: Among the total number of patients, 38.36% (n = 1316) was mutation positive. Mutation frequency for the general healthy population was 8%. Total number of patients with only SNPs (including non-synonimous SNP R202Q) were 1883 (54.8%). Accordingly, 80% of the patients were one single mutation carriers most of whom (about 85% of them) combined with a total of 19 different common and rare SNPs involving; exon 2- D102D, D103D, P124P, G138G, A165A, P180P, R202Q, and G219G; exon 3- R314R and S363S; exon 5- E474E, Q476Q, R501R, I506I, and D510D; exon 9- P588P; and exon 10- S683S, A701A and P706P. M694V accounted for the majority of FMF chromosomes (44%), followed by E148Q (19%), V726A (10%), M680I (8.3%), P369S (3.6%), R408Q (3.1%), K695R and R761H (2%), M694I and A744S (1%). Furthermore, novel mutations involving S141I,S166L, S179N, I506V, R151S, G340R, G456A and non-synonimous R202Q were in association with typical FMF phenotype when combining with a heterozygous mutation.

Conclusions: Molecular techniques, sample sizes, and ancestral regions should be regarded as critical and determinative keys in FMF clinical and molecular diagnosis in particular for the mutation negative and/or asymptomatic cases.

PS2-FRI-309

Recurrent (MPGN) membranoproliferative glomerulonephritis type 1 successfully treated with plasma exchange (PE)

P.Yadav* ¹, M.Ognjanovic¹, M.Coulthard¹, N.Moghal¹, H.Lambert¹, Y.Tse¹

¹Department of paediatric nephrology,Great North children Hospital,Newcastle upon tyne, UK

Objectve: Many kidney diseases recur after transplantation though risk of recurrence should not prohibit transplant. Type 1 MPGN recurs in 20–30% of patients although the incidence in children is even higher. It is more common in living related donation and typically presents with significant proteinuria. The incidence of graft loss at 10 years after recurrent disease is quoted at 14.4%.At a time when there is no established treatment modality for treatment of MPGN recurrence we report successful treatment with plasmapheresis.

Methods: A seventeen old girl had a live related transplant at age of 10. Eleven months after transplant she developed overt proteinuria. A transplant kidney biopsy revealed recurrence of MPGN with no features of acute rejection or chronic allograft nephropathy. She developed nephritic syndrome (protein creatinine ratios >500 mg/mmol) .She was treated with plasma exchange (18 sessions). Nephrotic syndrome resolved and proteinuria started to fall within days of treatment. However, few weeks later it reoccurred but did respond to PE and remained low since day 7. Estimated GFR was 45 ml/1.73 m².

Results: Six years after the first recurrence she continues to have good graft function with no proteinuria.

Conclusions: With better HLA matching and more potent immunosuppression recurrent glomerulonephritis presents the third most important cause graft failure. Currently, there is no available evidence based treatment for recurrent MPGN. We report excellent respond to PE. We would like to highlight the need for a collaborative multicentre study in PE in recurrent MPGN.

PS2-FRI-314

Nutcracker syndrome: an underdiagnosed cause for proteinuria in children?

I. Bilge¹, B. Yavas Aksu¹, S. Emre², A. Yılmaz* ¹, Z.N.Yürük Yıldırım¹, E.Yekeler², A. Sirin¹

¹Istanbul University Istanbul Medical Faculty, Pediatric Nephrology Department, Istanbul, Turkey, ²Istanbul University Istanbul Medical Faculty, Pediatric Radyology Department, Istanbul, Turkey

Left renal vein (LRV) compression between the aorta and the superior mesenteric artery, commonly referred to as the nutcracker syndrome (NS), is a rare condition resulting in renal venous hypertension. It has increasingly been recognized as a cause of proteinuria while the classic symptoms include left flank pain with hematuria.

We aimed to report our experience in the diagnosis and surgical treatment of the NS in 15 patients (13 girls) who had nondiagnostic investigations for many years before presentation. Mean age was 12.2 ± 2.4 years, and presenting symptoms were persistent orthostatic proteinuria (63.4%) (mean urine protein excretion was 493 ± 263 mg/day) and abdominal pain (36.6%). The kidney function tests, electrolytes,serum albumin, lipid profile, C3 levels, DMSA scintigraphy, BP measurements and the physical examination of all patients were normal. Renal biopsy had been performed in 1 patient, and she had received steroid and ACE inhibitor before admission to our instution. A diagnosis of the NS was suspected from the clinical examination and doppler ultrasound (US) in 11 patients, and confirmed by renal magnetic resonance (MR) angiography. In remaining 4 patients, while US findings were normal, MR angiography revealed LRV compression. Because of recurrent gross hematuria and proteinuria, one patient underwent LRV transposition, other patients with mild and tolerable symptoms were treated conservatively. During a mean of … months of follow-up (….. -…….), no improvement (6 patients) or only partial improvement (8 patients) was observed in patients receiving conservative treatment. In one patient who underwent LRV transposition, proteinuria had significantly decreased during follow-up.

The diagnosis of the NS has to be considered in children with persistent ortostatic proteinuria, and although renal doppler US is the first choice for the diagnosis, MR angiography may be necessary to confirm the dianosis in most cases. We strongly suggest that the patients should be followed up regarding symptoms and renal function to determine the clinical course and prognosis of NS. Appropriate diagnostic work-up and treatment may help alleviate patient morbidity from this chronic condition.

PS2-FRI-321

Unusual presentation of IgA nehpritis in a child

G. Parmaksız*¹, N. Cengiz¹, T. Canpolat², H. Özdemir³, E. Baskın⁴, A. Noyan¹

¹Baskent University School of Medicine, Departement of Pediatric Nephrology, Adana, Turkey, ²Baskent University School of Medicine, Departement of Pathology, Adana, Turkey, ³Baskent University School of Medicine, Departement of Pathology, Ankara, Turkey, ⁴Baskent University School of Medicine, Departement of Pediatric Nephrology, Ankara, Turkey

IgA nephropathy is also a risk factor for chronic renal failure in children. Microscopic hematuria and recurrent episodes of macroscopic hematuria are the most common clinical manifestations of the disease in childhood. We report, herein, a case with pulmonary symptoms together with renal disease. A 12-year-old girl presented with cough and diagnosed as pneumonia and revealed microscopic hematuria. She was treated with antibiotics and consulted to our clinic because of elevated blood pressure and hypocomplementemia (C3:67 mg/dl). On examination her blood pressure was 110/70 mmHg, and she had diffuse bilateral crackles, and pupil edema revealed at her left fundus. Initial laboratory testing revealed elevated mild azotemia (BUN:22 mg/dl, Creatinine: 1.09 mg/dl), hypoalbuminemia (2.4 gr/dl), mild anemia (Hb:8.4 gr/dl), elevated ESR, fibrinogen and CRP (ESR: 66 mm/h, Fibrinogen: 5.08 CRP: 15 mg/L). Serum C3 and C4 levels were normal (C3: 74 mg/dl, C4: 17.2 mg/dl), serum antinuclear antibody, antineutrophilic cytoplasmic antibody and antiglomeruler basement membrane antibody were all negative. Urine analysis revealed 3+ blood, 4+ protein (4.4 gr/L), 1+ leukocyte and Up: 114 mg/m2/h. Chest CT revealed interstitial infiltrations at left lung and atelectasis at right lung. Renal Doppler USG demostrated renal flow with high resistance. Echocardiography performed and revealed HT related septal ventricular hypertrophia. We performed renal biopsy and light microscopy analysis revealed 18–19 glomeruli. Six of them were globally sclerotic and 3–4 of them have crescent formation with endocapillary proliferation. Immunohistochemical staining showed 2+ mesangial staining with IgA and less intense staining noted with IgM(+), C3 (−/+) and C1q(−/+).

With this case report, we would like to underline one of the different presentations of IgA nephropathy and paediatricians should be aware of the lung involvement of IgA nephropathy.

PS2-FRI-322

Calcimimetic therapy in children with steroid-sensitive nephrotic syndrome

B. Schaefer*¹, J. Oh², F. Schaefer¹, B. Toenshoff¹, G. F. Hoffmann¹, C. P. Schmitt¹

¹Center for Pediatric and Adolescent Medicine, Heidelberg,Germany, ²University Children’s Hospital, Hamburg, Germany

Background: CaSR is expressed in human podocytes. In vitro, activation of the CaSR stabilizes the actin cytoskeleton and reduces apoptosis, and, in vivo, attenuates proteinuria, podocyte and GFR loss and glomerulosclerosis. Clinical data have not yet been obtained.

Methods: 4 children (3–9 years) with idiopathic nephrotic syndrome (NS), who showed up with initial manifestation (n = 2) and second relapse (n = 2), respectively, and who objected to steroid therapy, were treated with the calcimimetic Cinacalcet (Cin). Initial dose was 15 mg/m²BSA/d, gradually increased by 5 mg/m²BSA according to the antiproteinuric effect. Calcium was supplemented at an initial dose of 2 × 500 mg/m²BSA/d.

Results: The first patient received a single dose of Cin (5 mg/m²). Protein- and albuminuria were reduced (570 to 398 and 378 to 255 g/mol crea) within 24 hours (normal range <20 and <3). In the remaining 3 patients proteinuria was 1618, 821 and 763 g/mol crea and declined by 92, 71 and 73% to a nadir of 130, 235 and 209 within 8, 5 and 3 days. Albuminuria was 1347, 648 and 746 g/mol crea and declined by 96, 73, and 76% to a nadir of 58, 172 and 178. Serum albumin was 26.7, 26.9 and 29.1 g/l and increased to a maximum of 27.4, 28.6 and 31.8. Oedema disappeared in all 3 patients within 6–13 days. Ca++ − and phosphate excretion did not change; serum Ca++ remained in the normal range. The maximal doses of Cin were 26.1, 21 and 28.3 mg/m²BSA, the treatment was well tolerated. All 3 children experienced a relapse after 10, 23 and 19 days; which was associated with an upper airway infection in 2 patients. Cin was discontinued and prednisolone therapy initiated, which induced remission in all 3 patients within 7–9 days.

Conclusions: Cinacalcet markedly reduces proteinuria in children with idiopathic NS, albeit without inducing a complete and stable remission.nephropathy and paediatricians should be aware of the lung involvement of IgA nephropathy.

PS2-FRI-331

Risk factors for urolithiasis in infants

O. Bagcı¹, N. Canpolat*², I. Adaletli³, Y. Ozpeynirci³, M. Kucur⁴, S. Caliskan², L. Sever²

¹Department of Pediatrics, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey, ²Department of Pediatric Nephrology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey, ³Department of Pediatric Radiology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey, ⁴Department of Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey

Objectives: Studies on urolithiasis in infancy are limited and mostly retrospective. The aim of this prospective study is to analyze the risk factors for urinary stone formation in this particular age group.

Methods: Thirty patients under 2 years of age, suffering from urolithiasis and 30 healthy controls were prospectively enrolled. Demographic features, family history for urolithiasis, nutritional characteristics, medications and presenting symptoms were recorded. Laboratory studies included serum biochemistry, blood-gas analysis, urinalysis, Na-nitroprusside test, urinary calcium, citrate, oxalate, urate, creatinine levels, urinary culture and ultrasonography.

Results: Mean age was 11.1 ± 5.4 and 11.3 ± 5.3 months in patients and healthy controls, respectively. Male/female ratio was 1.7:1 in patients and 1.3:1 in controls. Positive family history were noted in 47% of the patients and in 10% of the controls (p = 0.003). The most frequent presenting symptom was restlessness. Nutritional characteristics were not significantly different between the two groups. Urinary tract infection was detected in 10% of patients, which did not reach statistical significance when compared with controls. Overall 59 stones were detected in 30 patients. 95% of the stones were located in upper urinary tract; 37 (63%) were >3 mm in diameter. 16 patients had multiple stones, and in 8 of these, stones were bilateral. At least one metabolic abnormality was detected in 23 (77%) of the 30 patients and in 8 of the 30 controls considering classical reference values. The most frequent metabolic abnormality was hypercalciuria. Frequencies of hypercalciuria and hypocitraturia were significantly higher in the patients (p = 0.015, p = 0.020 respectively), however urinary Ca/Cr, citrate/Cr, oxalate/Cr and urate/GFR levels did not differ significantly between the patients and controls.

Conclusion: Hypercalciuria and hypocitratuira seem to be significant risk factors in the pathogenesis of urolithiasis in infants. Classical reference values used for metabolic evaluation of urinary stone disease may not be valid for this particular age group

PS2-FRI-332

Nephrogenic syndrome of inappropriate antidiuresis caused by a gain-of-function mutation in the vasopressin V2 receptor gene

M. Hansen¹, V. Frank², M. Schröder¹, H. Bolz², K. Latta¹, C. Bergmann*²

¹Clementine Kinderhospital, Frankfurt, Germany, ²Bioscientia Center for Human Genetics, Ingelheim, Germany

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is an X-linked disorder of water/electrolyte balance caused by an AVPR2 gain-of-function mutation that leads to constitutive activation of the encoded vasopressin V2 receptor. Defective urine dilution results in eu-/hypervolemic hyponatremia resembling the syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).

We report a Turkish family with NSIAD. Initial serum natrium of the six-month-old proposita was 131 mmol/l, after intravenous fluid infusion it declined to 126 mmol/l. High amounts of NaCl (about 9 mmol/kg) had to be continuously substituted. Her low serum osmolarity (273 mosmol/l) was in contrast to high urine osmolarity (424 mosmol/l). After discharge, NaCl substitution was continued, first a salt-wasting tubulopathy was supposed which was in contrast to euvolemic hydration status. The girl’s father had a hyponatremic seizure in infancy; a salt loosing tubulopathy was supposed in him too. Hyponatremia recently re-occurred during surgery, but otherwise he gets along by drinking only very little. The father’s brother also experienced recurrent hyponatremia. We suspected NSIAD in this family, sequenced the AVPR2 gene, and were able to identify the heterozygous missense mutation c.409C > T (p.Arg137Cys) in the proposita, subsequently shown to segregate with the phenotype in her father and uncle. This mutation is one of the typical AVPR2 gain-of-function mutations leading to NSIAD. The patient’s sister also carries the mutation, but is clinically fine most likely due to favourable X-inactivation of the mutant allele, recently corroborated by an unremarkable water loading test performed in her.

Given that patients benefit from NSIAD treatment with fluid restriction and osmotic diuresis with orally taken urea, an early diagnosis is helpful to protect them from episodes of severe hyponatremia. In conclusion, NSIAD should be considered in patients with recurrent or persistent eu- or hypervolemic hyponatremia and can be easily confirmed by sequencing of the small AVPR2 gene.

PS2-FRI-338

Poliarteritis nodosa: a case presenting with renal mass

N. Cengiz* ¹, G. Parmaksız¹, S. Demir², L. Oguzkurt¹, E. Baskın³, A. Noyan¹

¹Baskent University School of Medicine, Department of Pediatric Nephrology, Adana, Turkey, ²Baskent University School of Medicine, Department of Radiology, Adana, Turkey, ³Baskent University School of Medicine, Department of Pediatric Nephrology, Ankara, Turkey

Polyarteritis nodosa (PAN) is a typically multisystem, chronic, relapsing disease resulting from vascular inflammation, often leading to aneurysm formation. Skin, abdominal viscera, kidneys, and central nervous system are predominantly involved. It may represent different clinical presentations. Herein, we report an adolescent girl presented with renal haematoma. Case: A 15-year-old girl was admitted to our unit with complain of fever and abdominal pain for 20 days. Laboratory findings revealed leucocytosis, elevated erythrocyte sedimentation rate and CRP. Serologic tests including ANA, AntiDNA, and ANCA were negative. Abdominal ultrasonography and tomography showed 96 × 53 mm, heterogen solid nodular mass lesion in the center of left kidney. According to USG and CT images, this mass may be consistent with renal abscess or haematoma. The mass was punctured, and neither found blood nor purulent material. Abdominal MRI demonstrated a subcapsular haematoma in the left kidney, and left lobe of liver, and surrenal gland. MRI findings suggested vasculitis because of multiple haemorrhages in different localizations. Multiple aneurysm formations in both kidneys, liver, celiac arteries and left lung were revealed by conventional angiography. Vasculitic syndromes may have insidious clinical symptoms and should be considered in patients with multiple organ involvement.

PS2-FRI-345

Mycophenolate mofetil (MMF) treatment in childhood nephrotic syndrome- own observations

A.Medynska*¹, K. Fornalczyk¹, K. Kilis-Pstrusinska¹, A, Jakubowska¹, D. Zwolinska¹

¹Dept. of Paediatric Nephrology, Medical University, Wrocław, Poland

Many children affected with nephrotic syndrome (NS) fail to obtain remission despite treatment based on the combination of steroids, alkalyting agents and/or cyclosporine A (CsA). In patients with relapsing NS and those with serious side effects to previous treatment, MMF is regarded to be useful in achievement and maintenance of complete or partial remission.

The aim of the study was to assess the efficacy of MMF in children with NS.

We reviewed the medical records of 14 children with NS on MMF treatment hospitalized in our department, among them: 10 girls and 4 boys, aged: 8 to 17 years (mean 13,2 yr).

In all patients renal function was normal (GFR >90 ml/min/1.73 m²pc). The histological findings were as follows: FSGS- 5 , MCD- 2, mesangioproliferative GN- 1, mesangiocapillary GN-3. In 1 case renal biopsy was not performed. Prior to MMF institution patients were treated with steroids, alkalyting agents and CsA. Children were divided in 2 groups regarding the course of NS: I steroid- dependent (8 children: 5 girls, 3 boys)and II steroid- resistant NS(6 children: 5 girls, 1 boy).

MMF was started with no response to previous treatment or in the presence of steroid or CsA toxicity. The follow-up period lasted from 1 to 11 months (group I- mean 7.1 mth, II-6.25 mth). MMF is continued in 6 children with steroid- dependent NS. In others therapy was stopped for the lack of remission (4) or presence of adverse effects (3). In 1 patient pancreatitis was observed, the condition resolved spontaneously after MMF withdrawal. In conclusion, MMF in combination with tapered dose of steroids is useful in maintenance of remission in steroid- dependent NS, whereas its efficacy in steroid- resistant NS remains doubtful.

PS2-FRI-351

Role of NPHS1, NPHS2 and WT1 gene mutations in congenital and steroid-resistant nephrotic syndromes: a descriptive study

M. Muñoz* ¹, A. Martinez¹, A. Madrid¹, E. Ars², C. Herrero¹, S. Chocrón¹, L.E. Lara¹, R. Vilalta¹, J.L. Nieto¹

¹Paediatric Nephrology Department. Vall d’Hebron Hospital, Barcelona, Spain, ²Molecular Biology Laboratory,Puigverd Foundation, Barcelona, Spain

Introduction: Nephrotic syndrome (NS) is a primary disorder of the glomerular filtration barrier. Recent studies show possible involvment of podocyte and slit diaphragm proteins’ gene mutations in the pathogenesis of steroid-resistant nephrotic syndrome (SRNS).

Objetives: The aim of our study was to determine the prevalance of NPHS1, NPHS2 and WT1 gene mutations in cohorts of 29 SNRS children and 5 children with Congenital NS (CNS), and establish a genotype/phenotype correlations.

Methods: We performed direct exon sequencing of NPHS1, NPHS2 and exons 8 and 9 of WT1.

Results: 11 of our patients had a mutation in the scanned genes (6 SRNS and 5 CNS). NPHS1 mutation accounted for all CNS cases and for 34% of the SRNS patients, with NPHS2 (55%) and WT1 (16%) completing the SRNS genetic profile.

43% (3/7) of NHPS1+ patients underwent renal transplant, two of them secondary to end-stage renal disease (ESRD) and one for intractable proteinuria. Of the remaining four, two are pending transplantation and the others are controlled by antiproteinuric treatment without renal failure. Transplanted patients remain disease free.

The clinical presentation of all NPHS2+ patients was SRNS. Two underwent pre-emptive renal transplantation for failure to thrive secondary to intractable massive proteinuria, with the third reaching adolescence without ESRD. All NPHS2 and WT1 mutations had focal segmental glomerulosclerosis on biopsy.

WT1+ patient, debuting as Denys Drash Syndrome (Wilm’s tumor and gonadal atrophy), was transplanted within 4 month of diagnosis, with no recurrence.

CONCLUSIONS: All CNS patients proved NPHS1+, whereas NPHS1, NPHS2 and WT1 were the culprit in older children with SRNS. Scanned genes accounted for only 20% of SRNS group. We recommend avoiding steroid treatment according to lack of response in this group. We consider failure to thrive secondary to intractable proteinuria as an indication for pre-emptive transplantation. We had no disease recurrence post-renal transplant.

PS2-FRI-354

What’s new in the treatment of the minimal change nephrotic syndrome?

A. Boueva*¹, G. Zlatanova¹

¹University Pediatric Hospital, Sofia, Bulgaria

Introduction: The proper treatment of the first episode of minimal change nephrotic syndrome (MCNS) is considered by many to be crucial for its progress. This to a very large degree determines the prognosis of the disease. A cumulative dose of corticosteroid has been administered at the first episode of MCNS in recent years. Observation of the above treatment, show that the use of high cumulative dose reduces the percentage of children with relapses during the first 2 years after cessation of treatment.

Material and methods: 14 patients with a first episode of MCNS have been treated with a cumulative dose of prednisolon- 3400 mg/m2. Eight boys and six girls, diagnosed with a first episode at ages 16 months to 6 years. Corticosteroid p.o was the only treatment for all children. Follow-up period lasted from 18 to 24 months after cessation of treatment.

Results: All children developed infection of the upper airways during the follow-up. 2 of the 14 children had a single relapse during observation (14.2% relapses), in the rest the urine was negative for protein during the illness (85.7% remission). The relapses were easily treated- urine became negative for protein in 3 days.

Conclusions: The treatment of MCNS with a cumulative dose of 3400 mg/m2 corticosteroid leads to low relapses and high remissions rate during the first 2 years after the earliest episode.

PS2-FRI-363

Albumin excretion fraction for monitoring proteinuria when protein plasma level is manipulated

G. Ardissino* ¹, F. Te^l1, A. Monzani², S. Testa¹, F. Paglialonga¹

¹Pediatric Nephrology Unit, IRCCS Fondazione Ca’ Granda Ospedale Maggiore, Milano, Italy, ²Dept.of Pediatrics, IRCCS Fondazione Ca’ Granda Ospedale Maggiore

Urinary protein/creatinine ratio (uPr/uCr) or protein excretion rate are the most common indicators for monitoring NS and the efficacy of treatments. However, these indicators are very much influenced by changes in plasma protein level induced by plasma or albumin infusion as well as by plasmaexchange (PEX). In these conditions, it becomes difficult to detect improvement, as a response to treatment, since the increase in plasma protein per se causes an increase in proteinuria. As an exemple, in a 12 yo boy with clinically stable FSGS without specific treatment but weekly albumin infusion, uPr/uCr was 15, 95 and 34 at baseline, 1 hr and 24 hrs after albumin infusion, respectively.

In the present paper we explore the working hypothesis that albumin excretion fraction (FeAlb) is more accurate for measuring proteinuria whenever plasma proteine level is manipulated. A 19 yo girl with FSGS unresponsive to standard treatment (steroids, tacrolimus) was addressed to high volume PEX with albumin solution 4.5 gr/dL (thrice weekly). Following the first few sessions of PEX, uPr/uCr ratio increased (from 11 to 15) as a consequence of the increase in plasma protein level induced by PEX itself. Following are the basic laboratory before, during and after the PEX treatment. After the 3rd PEX the efficacy of the treatment was clearly detected by FeAlb but not by uPr/uCr (line 4 in Table).

Day sAlbumin uPr/uCr FeAlb

0 (Baseline) 1.7 11.3 8.9

6 (PEX 2) 2.5 14.9 10.8

7 (PEX 3) 2.7 15.0 8.2

11 (PEX 4) 2.4 11.3 4.8

14 (PEX 5) 2.9 7.7 2.7

20 (PEX 6) 3.1 8.9 2.4

26 2.9 4.4 1.3

In conclusion in selected conditions (whenever plasma protein level is manipulated), FeAlb seems a better indicator of protein loss than protein excretion rate or uPr/uCr. More studies are needed to test its efficacy.

PS2-FRI-365

The pathological signs of lupus nephritis activity

I. Kazyra*¹, A. Sukalo¹, T. Letkovskaja¹, V. Savosh¹, N. Tur²

¹Belarus State Medical University, 1st Chair of Pediatrics, Minsk, Republic of Belarus ²2nd Children’s Hospital, Department of Nephrology, Minsk, Republic of Belarus

The purpose of our study was to reveal possible relationships between number of glomerular dividing cells, lupus nephritis (LN) activity and its anticipated clinical course.

Methods: We analyzed renal biopsy specimens obtained from 10 patients with LN over the last 4 yr from the Republic Center of Pediatric Nephrology and Renal Replacement Therapy, Minsk, Belarus. Proliferation activity was examined by immunohistochemistry using monoclonal antibodies to protein Ki-67 (DAKO Cytomation, Denmark). The quantitative assessment of Ki-67-positive cells in glomerular and extraglomerular areas was performed.

Results: To characterize the protean renal manifestations of systemic lupus erythematosus (SLE) we used the classification of the International Society of Nephrology (ISN) and the Renal Pathology Society (RPS) (ISN/RPS classification, 2004). The class IV of LN was described in 9 of 10 cases. The activity index was generally high and varied from 6 to 14. We found out morphology of class III only in one patient (activity index was 4). The immunostaining with antibody to Ki-67-protein was detected in glomerular and areas of extraglomerular proliferation. The analysis of quantitative assessment of dividing cell showed statistically significant (p = 0,00813) positive correlation between the number of Ki-67-positive glomerular cells and activity index of LN. A highly significant correlation was also evident between the mitotic activity of glomerular cells and the clinical and laboratory activity manifestations such as anemia, thrombocytopenia, visceral and skin lesions. (p = 0,026).

Conclusion: The increased number of Ki-67-possitive glomerular cells in cases with active LN, suggests the mitotic activity index as a possible factor of severe course fro SLE and in the presence of a greater number of observations can be used as a prognostic factor of the disease.

PS2-FRI-367

Combined ultrafiltration and plasmaexchange for patients with steroid resistant nephrotic syndrome

G. Ardissino* ¹, F. Paglialonga¹, V. Scarfia¹, S. Testa¹, A. Biasuzzi¹, M.E. Albion¹, G. Bagnaschi¹, C. Felice Civitillo¹, F. Tel¹

¹Pediatric Nephrology Unit, IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy

Plasmaexchange (PEX) is one of the possible treatment strategies for steroid resistant nephrotic syndrome (SRNS), in particular when associated to focal segmental glomerulosclerosis. Most of the patients with SRNS becomes resistant to diuretics and the management of their fluid overload sometimes becomes a major clinical challenge.

Here we describe our experience with combining ultrafiltration (UF) together with plasmaexchange aimed at removing part of the fluid overload in patients with SRNS undergoing PEX for other indications.

The described procedure was performed in 2 patients, a boy and a girl, 11 and 19 years old, with a baseline body weight of 39 and 80 Kg and an estimated overhydration of 3 and 16 Kg, respectively. The total number of PEX sessions was 7 for the boy and 5 for the girl.

PEX treatment (BM25 device) was performed with a substitution of 150% of plasma volume (10 with albumine in Ringer Lactate, 2 with fresh frozen plasma) in 3–6 hrs. Heparinization schedule was an initial bolus of 40–50 U/kg followed by 20 U/Kg/hr. On the arterial line, just before the plasmafilter (Gambro PF2000N), a hemofilter (Edwards Lifesciences HF 0.3) was placed, with a single line out for collecting and measuring ultrafiltrate. The UF volume obtained ranged between 320 and 2800 mL/session (equal to 2 to 7 mL/kg/hr), the Qb was 80–120 ml/min. The UF was well tolerated, hematocrit (monitored by CritLine2000) remained stable during the sessions. No significant adverse events were observed, except urticarial reactions. Only one session was complicated by increased transmembrane pressure requiring treatment discontinuation. The combination of UF and PEX is feasible, safe and efficacious and it represents an additional tool whenever fluid removal is necessary in patients unresponsive to diuretics and requiring PEX.

PS2-FRI-372

Proteinuria screening in children

A.Boueva*¹, S. Marinova¹, D. Roussinov¹, P. Miteva¹, M. Gaydarova¹, G. Zlatanova¹, S. Stefanov¹, T. Lisichkova¹, S. Ganeva¹

¹University Pediatric Hospital, Sofia, Bulgaria

Introduction: Screening for renal diseases in children was performed in Bulgaria and we investigated the prevalence of urine abnormalities, especially proteinuria. We also checked the blood pressure, BMI and made US of the kidneys . The prevalence of proteinuria was 3,4%. METHODS: 1650 healthy children (from 1 to 17 years with mean age 7,36 ± years , 720 girls, 930 boys) were investigated for proteinuria. They were instructed to completely empty the bladder at night, and early morning urine was sampled to be screened. The positive reactions were defined as 1+ (0,3 g/l). We divided the children in 5 groups: group I-early childhood (1–3 years), group II-preschool age (4–6 years), group III- early school age (7–10 years), group IV-middle school age (11–13 years), group V-adolescents (14–17 years) and those with or without obesity comparing BMI.

Results: The incidence of proteinuria in the different age groups was between 2,35% and 5,4% In the total population the incidence was 3,4%. There was no significant difference between the incidence in the different age groups. The prevalence of proteinuria in obese children (BMI >97 percentile) was 2,7% and was higher than in non-obese children 4,3%.

Conclusions: The screening program is effective for detecting the earliest signs for renal diseases. Proteninuria is one of the markers for kidney damage, especially in obese children.

PS2-FRI-380

Multiple-hit scenario and improved genetic testing by next-generation sequencing in patients with atypical hemolytic uremic syndrome (aHUS)

N. Bachmann¹, T. Eisenberger¹, A. Melk², B. Kranz³, N. Wirtz⁴, H. Fehrenbach⁵, K. Häffner⁶, L. Pape², H.J. Bolz¹, C. Bergmann*¹

¹Bioscientia Center for Human Genetics, Ingelheim, Germany, ²Hannover Medical School/ Clinic for Paediatric Nephrology, Hepatology and Metabolic Disorders, Hannover, Germany, ³University Hospital Münster, Department of Pediatric Nephrology, Münster, Germany, ⁴Department of Nephrology, Trier, Germany, ⁵Department of Pediatric Nephrology, Memmingen, Germany, ⁶University Hospital Freiburg, Department of Pediatrics, Freiburg, Germany

Hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and impairment of renal function, and is the most common cause of acute renal failure in childhood. Most cases occur secondary to bacterial infection, whereas about 10% of HUS patients are classified as atypical (aHUS) with a generally poorer prognosis. Genetic complement abnormalities play a major role in aHUS and lead to uncontrolled overactivation of the alternative complement pathway. While the glomerular vasculature of the kidney is the main target, about 20% of patients additionally show extrarenal involvement.

There is increasing evidence for a multiple-hit scenario in aHUS with complex inheritance, i. e. mutations in genes encoding complement regulatory proteins or complement activators predispose to aHUS rather than being clearly causative per se. According to the guidelines of the European Paediatric Study Group for HUS, genetic testing of CFH, CFI, MCP, THBD, CFB and C3 is indicated in all patients with aHUS, even if plasma levels are normal. Genotype-phenotype correlations make genetic testing an essential part of clinical management; the genetic predisposition often determines the prognosis after the initial HUS episode and after renal transplantation. We present our molecular findings in patients with aHUS. Our data corroborate that many patients carry an alteration in more than one gene which may aggravate the clinical phenotype in line with a mutational load model. These results emphasize the need to test all genetic susceptibility factors which, however, is laborious and expensive with current sequencing techniques. As solution to this dilemma, new sequencing technologies (so-called Next-Generation Sequencing, NGS) allow simultaneous investigation of multiple genes in a time- and cost-efficient manner. We will present a novel genetic testing approach based on NGS that will considerably improve genetic diagnostics and clinical management of patients with aHUS.

PS2-FRI-392

Body height of children with nephrotic syndrom (NS)

L. Stakhurlova*¹, V. Sitnikova¹, T. Nastausheva¹, E. Kulakova¹, O. Minakova¹, A. Shvirev¹, O. Simonova¹, N. Nastausheva¹

¹Voronezh State Medical Academy, Voronezh, Russian Federation

Objectives and study: Aim of the study was to evaluate linear growth of children with NS according to LMS model and compare it with the linear growth of children\’s population of Voronezh region. We investigated linear growth of 70 children with steriod-sensitive NS of different age (from 2 to 15 years) and sex and 12000 healthy children.

Methods: For comparative analysis of children’s phisical development Z-score were used as normally distributed among random variables with zero mean and unit dispersion.

Results: There were noticed the changes of Z-scores of linear growth from −3.1 to 4.4 in children with NS. The growth was normal (from 25 to 75 percentile) in 41 (58.7%) of children; below 25 percentile—in 8 (25.5%)of patients and above 75 percentile—in 21 (31.0%) of children with NS.The mean of growth Z score was 0.6 + −1.7 in girls and 0.3 + −0.8 in boys. We analysed the dosage and duration of prednisolone in NS children with different height (below 25 percentile, 25–75 percentile, above 75 percentile). No connections between the linear growth and dosage as well as with duration of prednisolone in children with NS were observed (H = 2.2, p = 0.33; H = 0.3, p = 0.87 respectively).

Conclusion: Our research shows no evidence of short stature of patients with NS and influence of prednosolone on their linear growth.

PS2-FRI-393

Renoprotective effect of angiotensin converting enzyme (ACE) inhibitors in diabetic children

T. Nastausheva*¹, M. Bobrov¹, L. Stakhurlova¹, A. Nastausheva¹, E. Stenshinskaya¹, O. Gurovich¹, O. Shatokhina¹

¹Voronezh State Medical Academy, Voronezh, Russian Federation

Objectives and study: Aim of our study was to examine influence of ACE inhibitors on quantity and quality of proteinuria(Pt)in children with diabetes mellitus type1(DM1).We investigated 70 children with DM1 who had Pt or microalbuminuria(Ma)and divided them into two groups as randomly selected \“case-control\”.The case group-37 patients received ACE inhibitors(enalapril or lizinopril)2.5–10 mg/d for 3–12 months, 33children(control group)did not receive any ACE inhibitors. Age, sex, duration of DM1, 24 h Pt, blood parameters, dosage of insulin per kg/d were equal in two groups.

Methods: Pt was measured with pirrogalol red, Ma-by nephelometric method, uroproteunogramms(UPG)-by automatic poliacrilamid gel electrophoresis.UPG was evaluated as \“normal\”,\“glomerular\”,\“tubular\” or\“mixed\”.All parameters were examined before the treatment and in 1 year.

Results: Pt decreased from 126.4 + −84.1 mg/d to 95.3 + −28.3 mg/d, Ma decreased from 136.5 + −81.3 mg/l to 22.8 + −17.0 mg/l in the case group.Types of UPG changed after the treatment with ACE inhibitors: \“normal\” type appeared in 9(24.3% of patients) instead of 0% before study, p < 0.001; \“mixed\” type decreased from 64.9%(in 24 children) to 35.1%(in 13 children). Control group of patients did not exhibit any changes in Pt: at baseline it was 151.6 + −15.1 mg/d, in 1 year-167.7 + −24.9 mg/d, as well as Ma:62.0 + −20.5 mg/l and 82.2 + −16.5 mg/l respectively. The types of UPG also did not changed.

Conclusion: Renoprotective effect of ACE inhibitors in children with DM1 consists of reduction of Pt, Ma and \“mixed\” type of UPG.

PS2-FRI-394

Siblings with antenatal Bartter syndrome

M. Ćuk¹, Z. Puretić*², K. Bojanić¹, V. Sarnavka¹, D. Milošević¹, I. Barić¹

¹Department of Pediatrics, University Hospital Center and School of Medicine, Zagreb, Croatia ²Department for Dialysis, University Hospital Center and School of Medicine, Zagreb, Croatia

Introduction: Bartter syndrome is a heterogenous group of inherited monogenic diseases characterized by impaired transport of electrolytes in the thick ascending limb of the loop of Henle. Consequently, water and acid-base balance are affected. Polyhydramnion, preterm birth, polyuria, dehydration, polydipsia and growth retardation are usual clinical problems, as hypokalemia, metabolic alkalosis, hyponatremia, hypovolemia, hyperaldosteronism, hyperprostaglandinuria and hypercalciuria are common laboratory findings. Although two types of Bartter syndrome are clinically distinguished- antenatal and classic, six genetically defined types are known.

Cases report: Sister and brother at age 4 and 2 years are presented. They were both prematures born after 34 and 36 weeks of gestation and pregnancies complicated by polyhydramnios. Sister presented during the first postnatal days with polyuria, dehydration, hyponatremia 120 mmol/L, hypochloremia 80 mmol/L, transient hyperkalemia 5.8 mmol/L, afterwards hypokalemia 2.4 mmol/L and hypomagnesemia 0.38 mmol/L. At age of two months her body length and weight were <5th percentile, she was prone to dehydration and hyperthermia, had metabolic alkalosis (7.56), hyperbicarbonatemia (37 mmol/L;ref < 23), plasma renin activity-(PRA) 75 μg/L/h (normal <16), hyperaldosteronism (14787 pmol/L;normal < 2460), hypercalciuria (20 mg/kg/day;normal <5) and nephrocalcinosis. Prenatally, boy was treated by removal of excess amount of amniotic fluid. Postnatally, polyuria >10 ml/kg/h, hyponatremia (121), hypochloremia (88), transient hyperkalemia (6.5) which subsequently resolved, pH 7.64, aHCO3 32.8, PRA >25xnormal, aldosteron >5xnormal, hypercalciuria >3xnormal and nephocalcinosis were noted. At age 2.5 years he was -3SD for body height and weight.

Conclusion: Based on characteristic clinical and laboratory findings, siblings most likely suffers from Bartter syndrom type II caused by a mutation of KCNJ1 gene encoding ROMK, potassium-sensitive ATP-channel what will be tested. Presently, both children are treated with fluid (3×daily needs), electrolytes (according to laboratory findings) and indomethacin (orally-2 mg/kg/day). Although both children are having progressive chronic kidney failure, current therapy was shown to be effective, as yet at least to some extent (improved growth, halved diuresis, PRA and aldosteron).

PS2-FRI-396

Extracorporal shock wave lithotripsy (ESWL) in the management of stones in children with oxalosis, a single centre experience

E. Al-Abadi*¹, H. Chandran1, S. Hulton¹

¹Birmingham children’s Hospital, Birmingham, UK

Introduction: Extracorporal Shock Wave Lithotripsy (ESWL) is the first line surgical treatment for most renal stones but may result in long term parenchymal damage. Children with Oxalosis may be exposed to more frequent ESWL with an increased risk of parenchymal damage.

Aims: To evaluate the success of ESWL in treating nephrolithiasis in children with hyperoxaluria and (i)identify factors that may affect success of treatment (ii)identify the effect of ESWL on eGFR during childhood.

Methods: We retrospectively identified patients with oxalate stones due to Primary Hyperoxaluria and other causes. Data collected: age, gender, type of hyperoxaluria, preventive treatments, stone location, presence of nephrocalcinosis, number of ESWL treatments, and eGFR.

Results: 28 patients formed 52 stonesof which 23 were treated with ESWL. Ten stones improved and 13 did not following. Of the 23 stones,9 were upper pole,9 were lower pole,4 were pelvic and one ureteric. All pelvic and ureteric stones improved while 66.7% of upper pole stones and 89.9% of lower pole stones did not. 20% of primary hyperoxaluria type 1 stones (1/5) improved as well as 47% of those with type 2. The mean pre & post eGFR in those who improved was 98.82 and 104.7 respectively and 100.75 & 95.68 in the non improvers. The mean pre-ESWL stone size in the improved and not improved groups was 7.3 mm and 8.5 mm respectively.

Conclusions: ESWL was successful in treating pelvic and ureteric stones. Upper pole stones response was 3 times better than lower pole stones. Age and prior preventive treatment did not affect treatment outcome. Stones in children with PH2 were more than twice as likely as those with PH1 to respond. Stone size did not affect treatment outcome. eGFR was not affected by ESWL during childhood follow up.

PS2-FRI-403

Simultaneous analysis of serum cytokines in children with nephrotic syndrome

A. Wasilewska*¹, A. Rybi-Szumińska¹, W. Zoch-Zwierz¹, J. Michaluk-Skutnik¹

¹Department of Paediatrics and Nephrology, Medical University of Białystok, Białystok, Poland

Idiopathic nephrotic syndrome (INS) is a very common glomerular disease. Histological diagnosis reveals minimal change nephrotic syndrome (MCNS) or focal segmental glomerulosclerosis (FSGS). INS is an immune mediated process. However advances in molecular genetics and cell biology suggest that defects in podocyte function play an important role in pathogenesis of FSGS.

Purpose: Finding out whether simultaneous assessment of 12 inflammatory cytokines may serve as a diagnostic tool in distinguishing patients with MCNS and FSGS.

Methods: The examination was performed on a group of 6 children with INS divided into two groups: 3 patients with FSGS and 3 patients with MCNS. The control group consisted of 6 healthy children. Simultaneous qualitative evaluation of 12 cytokines was made using Multi Analyte ELISArray Kit, according to the instructions of the producer (Sabiosciences, USA).

Results: In patients IL-1A and IL-1B were elevated in all children with MCNS and 1 with FSGS. IL-2 was detected in 2 patients with MCNS and 2 patients with FSGS. IL-8 was found in MCNS patients. IL-10 was elevated in 1 of 3 patients with FSGS and 2 of 3 patients with MCNS. Increased level of IL-12 was found in 1 patient with MCNS. TNF-A was negative in one patient with MCNS and GM-CSF was detected in 2 of 3 patients with FSGS and in 1 patient with MCNS. From twelve tested cytokines only the level of IL-17 was increased in all nephrotic patients. IL-4, IL-6 and IFN-G were negative in all NS patients.

Conclusions: The results do not allow us to define a specific configuration of cytokines in patients with MCNS and FSGS. However some attention should be paid to IL-17, which was significantly increased in both groups of children in our study.

PS2-FRI-408

Efficacy and safety of cyclosporine A (CsA) and mycophenolat mofetil (MMF) in steroid-sensitive nephrotic syndrome (SSNS) in children

V. Obukhova ^*1, O. Shatokhina¹, M. Ignatova¹, V. Dlin¹

¹Research Institute of Pediatrics and Children Surgery, Moscow, Russian Federation

Objectives and study: the aim of study was to compare the efficacy and safety of CsA and MMF in children with SSNS.

Methods: We investigated 42 children with SSNS: 1st group (n = 26) children with steroid-depended nephrotic syndrom (SDNS), n = 15 and frequently relapsed (FRNS), n = 11, received CsA 3–5 mg/kg/d and 2nd group (n = 16) with SDNS (n = 12) and FRNS (n = 4), received MMF 30 mg/kg/d (2 g/d maximum). Both groups did not differ in age (mean 9.23 ± 3.53 y and 10.2 ± 4.8 y) and duration of NS (2.15 ± 1.06 y and 1.18 ± 0.60 y), respectively. Frequency of relapses (FR) of NS before our study was 2.8 ± 0.83 and 2.88 ± 0.96, respectively. The duration of follow-up was 1.8 ± 1.14 years.

Results: Remission of NS developed in all children in both groups. After treatment the FR of NS in group treated by CsA was higher compared with group treated by MMF (1.76 ± 0.98 and 1.30 ± 1.06), respectively. CsA-dependency was developed in 38% children with SDNS and not developed in cases of MMF therapy. Side effects of CsA were founded in 42% children: hypertrichosis in 19.2%; gingival hyperplasia in 15.4%; acute nephrotoxicity, hypertension and infection in 7.7%. Renal biopsy was performed in 14 (54%) children after 2 years treatment of CsA and from 1 (7.1%) revealed signs of nephrotoxicity. Side effects of MMF treatment were usually mild and detected in 31%: gastrointestinal symptoms in 18.8% and leucopenia in 12.5% of children.

Conclusions: CsA and MMF are effective, but MMF is more safety in children with SSNS.

PS2-FRI-410

Aliskiren in pediatric Bartter Syndrome: three case reports

S. Nóbrega*¹, M. Abranches², I. Castro²

¹Department of Pediatrics, Hospital Dona Estefânia, Lisboa, Portugal, ²Pediatric Nephrology Unit, Hospital Dona Estefânia, Lisboa, Portugal

Objectives: To analyze the efficacy of aliskiren to maintain potassium blood levels in three patients with Bartter Syndrome (BS) treated with large doses of oral potassium chloride.

Case 1: A 10-year-old boy was investigated at the age of one month for failure to thrive and vomiting. Molecular diagnosis confirmed BS type III (mutations in CLCNKB gene). Treated with oral potassium chloride supplements, (11 mEq/kg/day) with poor compliance and severe gastrointestinal side effects. At the age of eight, aliskiren 150 mg/day was added to the treatment. One month later, normal blood potassium levels (K + 3,8 mEq/L) were attained with 0,5 mg/kg/day of oral potassium. Now, he is no longer taking any potassium supplements and has normal potassium blood levels (4,2 mEq/l).

Case 2: A 10-year-old boy was investigated for short stature at the age of four. Along with a growth hormone deficiency, diagnosis of BS type III (mutations in CLCNKB gene) was established. Treatment with oral potassium supplements (6 mEq/kg/day) was poorly effective. At the age of 8,5 years, aliskiren 150 mg/day was added to the treatment and potassium supplements reduced to 1,7 mEq/Kg/day and maintained thereafter. Levels of blood potassium are now in normal range (3,8 mEq/L).

Case 3: An 8-year-old boy has been diagnosed with BS type I (SLC12A1/NKCC2) after several episodes of dehydration over the first 5 months of life. Oral potassium supplements reaching 6 mg/kg/day were unable to maintain normal potassium blood levels. During the last 16 months, aliskiren 150 mg/day lead to a reduction in potassium supplements to 1,09 mEq/kg/day with normalkalemia (4,2 mEq/L) and normal plasma renin activity.

Conclusions: Aliskiren seem to be an effective therapy to maintain potassium levels in different types of BS. As far as we know, these are the first reports of successful treatment of pediatric BS with a direct renin inhibitor.

PS2-FRI-412

Nephrotic syndrome: a single centre experience

H. Alpay*¹, N. Yildiz¹, I. Gokce¹, N. Biyikli¹, U. Altuntas¹, A. Ekberzade¹, M. Benzer¹

¹Marmara University Medical Faculty, Department of Pediatric Nephrology, Istanbul, Turkey

Nephrotic syndrome (NS) is a clinical entity characterized by proteinuria, hypoalbuminemia, generalized edema and hyperlipidemia. Although steroid-sensitive NS(SSNS) is the most common form of idiopathic NS in childhood, steroid resistant NS(SRNS), which may lead to renal function deteriotion, cause significant morbidity and mortality.

THE OBJECTIVE of this study was to evaluate the clinical and biochemical parameters and the histopathological distribution of our NS patients.

Patients and methods: A hundred and four children (44 girls, 60 boys) with NS were analyzed retrospectively.

Results: The mean age of the children was 6.3 ± 4.1 (0.1–4.1) years and 5.2 ± 4.5 (0.25–16.5) years at diagnosis. The mean follow-up was 3.7 ± 3 (0.1–12.3) years.

The most common clinical findings were generalized edema in 69(66.4%) in whom genital edema was observed in 5, periorbital edema in 23(22.1%), hypertension in 11(10.6%), and oliguria in four (3.9%) patients. Seventy one (68.3%) patients were steroid sensitive, 19 were (18.3%) steroid resistant (SRNS), and 14 were (13.4%) steroid dependent (SDNS) nephrotic syndrome.

Fourty seven patients underwent renal biopsy. The most common pathologic findings were minimal change nephrotic syndrome in 19 (40.4%), focal segmental glomerulosclerosis (FSGS) in 10 (21.3%), membranoproliferative glomerulonephritis in six (12.8%), membranous glomerulonephritis in one (2.1%) and IgA nephropathy in four (8.5%) patients. Ten patients with SRNS or SDNS were treated with cyclophosphamide and seven with cyclosporine A. Two patients with FSGS treated with mycophenolate mofetil (MMF) and one of them was treated with rituximab. These patients were unresponsive either to MMF and rituximab and are still in nephrotic state.

Conclusion: The most common type of NS were steroid sensitive NS and FSGS. Cyclosporine A seems to be the most effective therapy in SRNS. Mycophenolate mofetil and rituximab were not helpful in our very limited number of patients.

PS2-FRI-413

Oxidative stress in cystinosis patients

L. Guimaraes*¹, A.C. Seguro², M. Shimizu², M.H. Vaisbich¹

¹Instituto da criança—hospital das clinicas—FMUSP, São Paulo, Brasil, ²Medical Investigative laboratory 12—hospital das clinicas—FMUSP, São Paulo, Brasil

Objectives: To evaluate a marker of oxidative stress (serum TBARS)in cystinosis children and compare the results with those observed in healthy controls and correlate with renal function parameters.

Methods: This is a prospective study with 20 cystinosis patients aged under 18 years with CKD stage I to IV. The following renal function parameters were: serum creatinine, BUN and creatinine clearance estimated (ClCrE) by stature. Serum levels of TBARS, which are markers of lipid peroxidation, were measured and compared to controls.

RESULTS: the serum TBARS levels detected in controls were 1,6 +/− 0,04 nmol/ml and in cystinosis patients were 4,03 +/− 1,02 nmol/ml. There was a significant statistic difference between the plasma TBARS levels among the two groups (p < 0,0001). To verify the influence of renal function on the serum TBARS levels, we correlated this parameter with serum creatinine, BUN, ClCrE and stage of CKD. We detected no significant correlation between plasma TBARS levels and all these parameters.

Conclusion: In this study we could not correlate the TBARS levels with creatinine clearance, class of CKD, serum creatinine or BUN. Therefore, oxidative stress in cystinosis patients could be a result of intrinsic mechanism of the disease. This is the first study measuring a marker of oxidative stress in cystinosis patients serum.

PS2-FRI-415

Medullary nephrocalcinosis in infants

N. Printza*¹, S. Batzios¹, M. Bantouraki², V. Chatzidimitriou¹, A. Tsiga¹, E. Doulianaki¹, M. Ilunga¹, E. Tsoutsou¹, A. Ververi¹, F. Papachristou¹

¹1st Pediatric Departement, Aristotle University, Hippokration Hospital,Thessaloniki, Greece, ²Pediatric Radiology Unit, Hippokration Hospital, Thessaloniki, Greece

Objectives and study: Medullary nephrocalcinosis (MN)represents a radiological finding. In infants MN is rare, usually asymptomatic and may occur in a wide spectrum of clinical conditions. The objective of our study was to investigate the incidence, the symptoms and the causes of MN in hospitalized infants during 1-year period.

Methods: Patients’ files, hospitalized from January 2010–December 2010, were retrospectively investigated and evaluated in relation to their kidney ultrasound findings and those with MN were reviewed. The clinical characteristics, symptoms, family history, associated diseases, diet and medication intake in infants with MN are discussed.

Results: Six infants, 3 boys and 3 girls, were found, in whom MN was demonstrated by renal ultrasound. Patient’s age ranged between 1 and 9 months. Concerning their signs and symptoms on admission, 2/6 infants had vomiting, serious metabolic acidosis and electrolytes disarrangement, 1/6 infant had macroscopic hematuria, while in 3/6 infants MN was an incidental finding. Their family history was negative for nephrolithiasis/nephrocalcinosis. MN was unilateral in 2 patients, bilateral in 3 patients and 1 patient with unilateral nephrocalcinosis exhibited bilateral findings during the follow-up period. Diagnostic work up from blood and urine showed that 2 patients had type 1 renal tubular acidosis, 1 patient had hypercalciuria with hypermagnesiuria (possible familial hypomagnesemia with hypercalciuria and nephrocalcinosis—under genetic investigation), 1 premature infant had hypervitaminosis D and history of furosemide intake (he was still on vitamin D supplements), 1 patient was classified as idiopathic nephrocalcinosis since no cause was found and in 1 patient the radiological finding of MN was transient.

Conclusions: MN is mostly asymptomatic and depicts a renal finding of great importance which should be carefully evaluated, in infants. The above 6 cases in 1 year period serve as illustrative examples for exploring the various, common or rare, etiologies, that may lead to the presence of medullary nephrocalcinosis in infants.

PS2-FRI-417

Fanconi-Bickel syndrome syndrome due to previously not described homozygous mutation in the 10th exon of the SLC2A2 gene

R. Cerkauskiene*¹, A. Jankauskiene¹, B. Tumiene², A. Utkus²

¹Vilniu Vilnius University; Vilnius university childrens hospital, Vilnius Lithuania, ²Centre for Medical Genetic, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania

Background: Fanconi—Bickel syndrome (FBS, OMIM #227810) is one of the inborn errors of metabolite transport. It is due to deficiency of GLUT2, a facilitative glucose transporter, encoded by SLC2A2 gene (OMIM *138160). The most characteristic symptoms are fasting hypoglycemia with postprandial hyperglycemia and renal proximal tubulopathy with disproportionally high glucosuria.

Objective: To describe the case of FBS with a common previously not reported mutation in the SLC2A2 gene.

Case report: 2.5-years-old female, the third child in a non-consanguineous Lithuanian family, presented with growth retardation, rickets at 4 months, poor motor development and muscular hypotony. At the age of 10 months severe rickets, renal proximal tubular dysfunction, ketonuria, metabolic acidosis and hepatomegaly were found. Dental symptoms were delayed teeth eruption and dental caries. She suffered from multiple bone fractures. Disproportionately high glucosuria, fasting hypoglycemia with postprandial hyperglycemia suggested FBS. Homozygosity for 1-bp deletion in exon 11 (c.1469delA [p.K490SfsX24]) was found. Clinical improvement was observed at 2,5 years.

Conclusion: This novel SLC2A2 mutation results in characteristic FBS. Both parents were heterozygous for the detected mutation. Although they were not related according to the family tree extending to five generations the possibility of remote common ancestor can not be excluded because both of the parents came from the same area in Lithuania.

PS2-FRI-418

Complete remission of congenital nephrotic syndrome (CNS) on ACEI treatmen

T. Jarmoliński*^1,2, M. Zaniew¹, P. Górniak³, E. Urasińska⁴

¹Department of Pediatrics, Nephrology and Toxicology, District Children’s Hospital, Szczecin, Poland, ²Department of Pediatrics, Hematology and Oncology, Pomeranian Medical University, Szczecin, Poland, ³Department of Pediatrics, Regional Hospital, Sławno, Poland, ⁴Department of Pathology, Pomeranian Medical University; Szczecin, Poland

Objectives: CNS of non-infectious origin almost always leads to ESRD. Spontaneous or treatment-induced resolution of proteinuria is reported very seldom and difficult to explain. The aim of our study is to present a case report of 1,5-year-old boy with complete remission of CNS after 8 months of antiproteinuric and intensive symptomatic treatment.

Methods: The child was fourth son of young, healthy and non-consanguineous parents, admitted at the age of 2 months for sepsis and edema. On admission he had nephrotic proteinuria (urinary Pr/Cr ratio 29 mg%/mg%), serum protein 25 g/l, albumin 10 g/l and cholesterol 271 mg%. Hypochromic anemia with very low serum Fe level, hyperfibrinogenemia, low AT III, hypothyroidism and low IgG level were also found in blood examination. Congenital infection was ruled out. After recovery from sepsis Baby-port was implanted and treatment with daily albumin and furosemide infusions together with ACEI (enalapril 0,4 mg/kg b.w.), heparin, erythropoietin, thyroid hormone, iron, calcium, vitamin D, immunoglobulins and hyperalimentation started. Kidney biopsy showed mesangial cells proliferation with cystic dilatation of some renal tubules and genetic testing didn’t reveal mutation either in NPHS2 or WT1 gene (Dept. of Human Genetics, Univ. of Michigan Medical School, Ann Arbor, US).

Results: Within a month proteinuria dropped (urinary Pr/Cr 13 mg%/mg%) and serum albumin came back to normal level. After 2 months he was discharged on i.v. albumin 3 times/week and within next 6 months proteinuria disappeared and he went into complete remission. Albumin infusions were stopped and supportive treatment restricted. Currently he is 18-mo-old normal physically and mentally developed boy. He is still treated with ACEI and furosemide and need some iron, vitamin D and thyroxine supplementation.

Conclusions: Treatment with ACEI may lead to complete remission of CNS. It is however not clear whether and when the therapy should be withheld.

PS2-FRI-419

A combination of mild and severe mutations in ALPL gene causing hypophosphatasia of intermediate type

A. Jankauskiene*¹, R. Cerkauskiene¹, B. Tumiene², A. Utkus², E. Mornet³

¹Vilnius University, Vilnius university childrens hospital, Vilnius Lithuania, ²Centre for Medical Genetics, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania, ³Maastricht University Hospital, the Netherlands

Background: Hypophosphatasia is an inherited disorder characterized by defective bone and teeth mineralization. The disease is due to mutations in the ALPL gene. Variable clinical expression of the disease ranging from stillbirth to pathologic skeletal fractures in adult years reflects allelic heterogeneity in this disease.

Case report: A patient is a 4 year old female. A head deformity was noticed at that time (turricephaly) and progressed thereafter with premature closure of cranial sutures and fontanelles. Increased intracranial pressure developed and became symptomatic (bulging fontanelle, bilateral edema of optical nerve, exophthalmos, prominent subcutaneous veins, nausea and vomiting). Skeletal symptoms appeared at about 6 months of age with the signs of rickets and waddling gait. Dental symptoms included delayed eruption of deciduous teeth, premature loss of incisors and severe caries. These dental symptoms specifically pointed to a possible diagnosis of hypophosphatasia. Biochemical assays revealed low-normal serum alkaline phosphatase (37.3 UI/l, n.35–281 UI/l), significant hyperphosphaturia (fractional excretion 24.8%), and low serum intact PTH (1–6 pg/ml, n.10–69 pg/ml). Clearly increased phosphoetanolamine in urine was detected (152 μmol/mmol creat., n.0–21 μmol/mmol creat), plasma pyridoxal 5′-phosphate was also highly elevated (1233 nmol/l, ref. <100 nmol/l). Molecular genetic analysis of ALPL gene in the proband revealed mutation c.334G > A (G95S) of paternal origin and mutation c.571G > A (E174K) of maternal origin.

Conclusion: The mutation c.334G > A was previously observed in infantile hypophosphatasia while mutation c.571G > A is relatively common and mostly observed in mild cases of hypophosphatasia. Such a compound heterozygote was not previously described.

PS2-FRI-426

Clinico-pathological correlation in children with IgA nephropathy over twenty years

C. Brown* ¹, N. Sebire², S. Marks¹

¹Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Trust, London, UK, ²Department of Paediatric Pathology, Great Ormond Street Hospital for Children NHS Trust, London, UK

Objectives: A new Oxford histopathological classification system of IgA nephropathy (IgAN) has been developed from four features found to independently predict adverse outcome with different patterns of lesions seen in children, compared to adults.

Methods: Retrospective review of the validity and predictive value of the Oxford criteria in children with biopsy proven IgAN, diagnosed between 1991 and 2010. Exclusion criteria included Henoch–Schőnlein purpura, inadequate biopsy specimens with less than eight glomeruli, and insufficient clinical data.

Results: Thirty-one patients met the inclusion criteria. Median age at diagnosis was 12.8 years, range 2.8–15.0, with a male predominance. Median follow up time was 40 months. At diagnosis mean systolic BP was 107 ± 16 mmHg, median proteinuria as measured by urine albumin to creatinine ratio was 54.6 mg/mmol (IQR 18.2–149.2), and the mean eGFR was 97 ± 16 ml/min/1.73 m². The mean rate of renal function decline was 0.51 ± 11.7 ml/min per 1.73 m². 26 (83.9%) of biopsies had a mesangial score >0.5. Segmental sclerosis was present in 18 (58.1%) biopsies. Crescents were present in 4 (12.9%) biopsies. Endocapillary proliferation was noted in 1 biopsy. Tubulointerstitial damage was present in 12 (38.8%) biopsies but was mild, affecting <10% of the biopsy.

Analysis of rate of decline of renal function by multiple linear regression showed that mesangial hypercelluarity was significantly associated with rate of decline (p < 0.01). Of the clinical parameters, eGFR at time of biopsy was most strongly associated with decline in renal function (p < 0.01).

Conclusion: Mesangial hypercellularity had the greatest predictive value for decline in renal function, confirming the validity of this pathological variable. In our cohort segmental sclerosis did not predict adverse outcome suggesting differences between adult published reports. Tubulointerstitial damage and endocapillary proliferation were rarer events, suggesting that these variables may have more limited value in predicting outcome in paediatric biopsies of IgAN.

PS2-FRI-435

ATP6V1B1 and ATP6V0A4 genes mutations in Tunicians children with distal renal tubular acidosis

D. El Hayek^1,2, H. Bouzidi³, G. Perez de Nanclares², H. Soua⁴, J. Ben Chibani¹, G. Ariceta*⁵, A. Haj Khelil¹, L. Castaño²

¹Laboratory of Biochemistry and Molecular Biology, Faculty of Pharmacy, Monastir, Tunisia, ²Research Laboratory of Genetics, Cruces Hospital, University of The Basque Country, Bilbao, Spain, ³Department of Biochemistry, Hospital of Tahar Sfar, Mahdia, Tunisia, ⁴Department of Pediatrics, Hospital of Tahar Sfar, Mahdia, Tunisia, ⁵Pediatric Nephrology, Cruces Hospital, University of The Basque Country, Bilbao, Spain

Distal renal tubular acidosis (DRTA) caused by ATP6V1B1 & ATP6V0A4 genes mutations is characterized by defective H + secretion at the cortical collecting duct α-intercalated cell. ATP6V1B1 mutations are associated with early onset sensorineural deafness, whereas ATP6V0A4 are not. DRTA genetic diagnosis in Tunisian population has not been described.

Aim: To identify ATP6V1B1 and ATP6V0A4 molecular defects causing DRTA in Tunisians.

Methods: DNA extraction by phenol /chloroform, polymerase chain reaction amplification and sequencing. Population: 10 children (8 boys) from 8 families (7 consanguineous), diagnosed of DRTA at 3 months of life.

Symptoms: All suffered dehydration episodes, diarrhea, vomits, growth failure and diffuse nephrocalcinosis. At diagnosis labs showed metabolic acidosis (pH 7.23 ± 0.08, bicarbonate 10.7 ± 2.15), with alkaline urine (U pH 7.67) and hypokalemia (K 2.9 mEq/L), 8 patients were deaf. RESULTS: In 8 kindred from six families a frameshift ATP6V1B1 mutation, which consisted on Cytosine duplication at the 1155 site, producing a premature stop codon: c.1155dupC (p.Ile386fs) was diagnosed. This finding suggests that site to be a hot spot mutation. Another child from a different family had one novel substitution: a single nucleotide (G to C), at the acceptor splicing site c.175-1G > C at intron 3 of ATP6V1B1. Further, we first time described one child with an additional homozygous G deletion c.1221delG (p.Met408CysfsX10) in exon 13 of ATP6V0A4 gene. That frameshift mutation caused a premature stop codon that resulted in truncation of the protein (417 from 840 amino acids).

Comment: Genetic diagnosis in Tunisian population helps to better diagnose DRTA associated or not with hearing loss.

PS2-FRI-437

Indications and results of kidney biopsy in children: a seven year review

D. Paripović*¹, M. Kostić¹, D. Kruščić¹, B. Spasojević¹, G. Miloševski-Lomić¹, G. Basta-Jovanović², J. Marković-Lipkovski², Z. Smoljanić³, A. Peco-Antić¹

¹Nephrology Department, University Children’s Hospital, Belgrade, Serbia, ²Institute of Pathology, School of Medicine, University of Belgrade, Belgrade, Serbia, ³Radiology Department, University Children’s Hospital, Belgrade, Serbia

Objectives: To retrospectively investigate the most common indications for renal biopsy and to analyze distribution of pathological findings in the last 7 years in a tertiary pediatric hospital.

Methods: All patients who underwent renal biopsy (RB) in our hospital between 2004 and 2010 were included in the study. RB were performed under fluoroscopy with a biopsy gun by the same radiologist.

Results: 150 RB were performed on 132 patients. 53% of pts were girls. Median age was 12.4 years (interquartile range, IQR 8.0–15.6 years). RB provided adequate specimens in 89% of cases. Median number of acquired glomeruli was 13 (IQR 8–20).

Native kidneys were biopsied in 109 patients (72% of RB), and transplanted grafts in 41 patients (28%). The most frequent indications for RB in native kidneys were asymptomatic hematuria (35%), followed by nephrotic syndrome (30%), asymptomatic proteinuria (12%) and nephritic syndrome (7%). Common causes of primary glomerulonephritis were focal segmental glomerulosclerosis (16%), minimal change disease (13%), IgA nephropathy (11%) and mesangioproliferative glomerulonephritis (9%), while lupus nephritis (6%) and Henoch Schonlein nephritis (4%) were the leading causes of secondary glomerulonephritis.

Conclusions: RB is important for adequate diagnosis of kidney diseases. Epidemiology of glomerulonephritis in our report is similar to literature data of other Balkan countries.

PS2-FRI-447

Renal amyloidosis in epidermolysis bullosa

A. Kavaz¹, M. Ekim*¹, H. Dindar¹, Z.B. Ozcakar¹, S. Altugan Cayci¹, F. Yalcinkaya¹

¹Ankara University, School of Medicine, Pediatric Nephrology Department, Ankara, Turkey

Renal amyloidosis may developed as a complication of dermatoses,but epidermolysis bullosa (EB) complicated by nephropathy has been thought to be rare. We report a young girl with EB who died of renal failure due to systemic amyloidosis.

A 14-year-old girl with a history of recurrent blisters and erosions on her whole body and oral mucosa since birth. She had diagnosed as severe generalized EB and followed different centers. She was admitted to our hospital with dysphagia and diagnosed as eusofagial stenosis. On her pyhsical examination, she had widespread skin blistering and scarring, fusion and mutilation of fingers and toes. Laboratuary investigations revealed hypoalbuminemia (1 g/dl) and 3+ proteinuria(263 mg/m2/h). Renal amyloidosis was detected by kidney biopsy . Colchium and ACE inhibitors were began. After three months her renal function deteriorated and renal failure was developed . Despite dialysis, she is died 1.5 months later because of sepsis.

Nephropathy is a common and serious complication of EB. Renal amyloidosis may play an important role in its etiology. We recommend that patients with EB should be periodically screened for nephropathy due to amyloidosis by urinalysis.

PS2-FRI-451

Growth and renal manifestations in children and adolescents with Fabry disease included in the Fabry outcome survey (FOS)

G. Pintos-Morell* ¹, U. Ramaswami², R. Parini³, M. Rohrbach⁴, G. Kalkum⁵, M. Beck⁶

¹Dept of Paediatrics, University Hospital Germans Trias i Pujol, Badalona, Spain, ²Paediatric Metabolic Unit, Addenbrooke’s Hospital, Cambridge, UK, ³Dept of Paediatrics, San Gerardo Hospital, University Milano-Bicocca, Monza, Italy, ⁴Division of Metabolism, University Children’s Hospital, Zurich, Switzerland, ⁵Dept of Paediatrics, University Medical Center, Mainz, Germany, ⁶Dept of Paediatrics, University Medical Center, University of Mainz, Germany

Background: Patients with the classic form of Fabry disease (FD) usually present their first manifestations during paediatric age. These initial symptoms are mainly neuropathic pain (acroparaesthesia), gastrointestinal problems, hypohydrosis and fatigue, which in turn represent the main triggers for starting early enzyme replacement therapy (ERT). Kidney involvement in FD may commence during childhood but its progression is not well described.

Objective: We aimed to investigate the evolution of growth and renal parameters (estimated glomerular filtration rate (eGFR) and microalbuminuria [Malb]) in children and adolescents included in FOS, receiving or not ERT.

Methods: eGFR was assessed by the new Schwartz and Counahan-Barratt formulas, and Malb was considered positive for values >30 mg/g creatinine or >30 mg/24 h. The cohort consisted in 308 children from 1 to 18 years (boys = 149 and girls = 159) included in FOS. We also collected data on height as growth is a very important parameter of global health status in children.

Results: Overall, 148/308 (48%) were receiving ERT (63.7% of boys and 33.3% of girls). We observed a stable eGFR for the total cohort including patients after long-term ERT (up to 6 years). However, a substantial proportion of patients presented CKD II (eGFR 90–60 mL/min/1.73 m²), being almost 20% (16/82) at 18 years of age. Malb substantially increased after 14 years of age, in non-treated as well as treated patients. At 18 years, 23/38 patients (16 girls and 7 boys) had positive Malb. Almost all patients attained normal growth for age.

Discussion: In this cohort of children with FD, Malb substantially increased from 14 years of age whilst eGFR remains stable. Early institution of ERT with agalsidase-alfa for a long-term period (up to 6 years) is associated with an overall normal growth and stable eGFR, but does not seem to influence the progression of Malb.

PS2-FRI-453

Does rituximab induce hypogammaglobulinemia in the treatment of children with steroid dependent idiopathic nephrotic syndrome?

L. Delbe-Bertin*¹, T. Ulinsk^1,2

¹Pediatric Nephrology, Armand Trousseau Hospital, APHP, Paris, France, ²Université Pierre et Marie Curie, Paris 6, France

Rituximab (RTX) seems to be a promising strategy in steroid dependent idiopathic nephrotic syndrome (SDNS). RTX induces profound depletion of circulating B-cells, suggesting hypogammaglobulinemia as a potential side effect. We have retrospectively analysed immunoglobulin G (IgG) levels in 12 pediatric patients on RTX with a B-cell depletion of a minimum of 3 months (N = 12, age 7.9 years) and compared the results to 16 patients on oral immunosuppressive drugs such as mycophenolate mofetil and/or cyclosporine A (N = 16, age 5.7 years). Patients in both groups had high degree SDNS with comparable disease activity. All patients were in stable remission at the time points of IgG analysis. IgG levels in the RTX group before RTX introduction were 6.2 ± 1.0 g/L and were not different from the MMF/CyA group (8.2 ± 2.5 g/L). In the MMF/CyA group, 5 patients (mean age 4.3 years) had at least one episode of hypo IgG, in two among them, this episode was prolonged (>3 months), and only one required IgG supplementation. No complication was noted in patients with decreased IgG levels. In the RTX group, 8 patients had decreased IgG levels before RTX infusion. After RTX, hypo IgG persisted in 7 among those 8 patients. No decreased IgG plasma levels have been noted in patients who did not already have low IgG levels before RTX treatment. The degree of hypo IgG did not change in relation to the time of CD19 depletion or the number of RTX infusions. Two patients required IgG supplementation and one had a complication related to the decreased IgG level (aseptic meningitis). In conclusion, RTX does not seem to induce decreased IgG levels in SDNS. However, it seems to prolong pre-existing decrease of IgG levels.

PS2-FRI-460

Clinical course of children with nutcracker syndrome

D. Alaygut*¹, M. Torun Bayram¹, A. Soylu¹, H. Çakmakçı¹, M. Turkmen¹, S. Kavukçu¹

¹Dokuz Eylul University, Medical Faculty Department of Pediatrics, Izmir, Turkey

Introduction: The classic symptoms of nutcracker syndrome (NS) include left flank pain with gross/microscopic hematuria and proteinuria. We aimed to evaluate the presenting symptoms and clinical course of our patients with NS.

Methods: We retrospectively analyzed the files of the children with nutcracker syndrome for the following parameters: Gender, age, complaints, urinalysis findings, accompanying illnesses, body mass index (BMI) and clinical course.

Results: There were 23 patients (12 girls; 2 posterior NS) with a mean age of 141 ± 36 months. While 17 of the patients presented with one or more complaints as malaise (1), loin pain (8), abdominal pain (7), varicocele (2) and macroscopic hematuria (9), 6 patients were diagnosed upon evaluation for microscopic hematuria or non-nephrotic proteinuria detected during routine urinalysis. Urinalysis revealed isolated proteinuria (7), isolated hematuria (15) or combined hematuria and proteinuria (9). Fifteen patients had proteinuria being non-nephrotic in all cases (8 ortostatic, 7 persistent). The diagnosis was made by Doppler ultrasonography in all patients. Six patients had accompanying hypercalciuria, while 3 patients had glomerular pathology (2 IgA nephropathy, 1 mesangial proliferative glomerulonephritis). During a mean follow-up period of 16 ± 22 months, proteinuria and hematuria decreased in 4 and 8 patients, respectively. Varicocelectomy was performed on 2 patients with varicocele. Mean BMI of the patients at last visit was significantly increased compared to BMI at diagnosis (19.1 ± 4.1 vs 18.4 ± 3.2, p = 0.028). BMI of the patients with decreased proteinuria and/or hematuria also increased during follow-up being significant in the latter group (18.7 ± 4.6 vs 17.0 ± 4.0, p = 0.028).

Conclusion: NS may present with symptoms or may be asymptomatic and detected upon urinalysis findings. Regression of hematuria and proteinuria seem to be related to increase in body mass index. Presence of other glomerular/non-glomerular causes of hematuria or proteinuria does not exclude NS.

PS2-FRI-461

Early diagnosis of deap-hus followed by complete renal recovery: case report

M. Aguirre¹, J. Mateos², C. Abarrategui³, J. López-Bayón⁴, M. López-Trascasa³, G. Ariceta*¹

¹Pediatric Nephrology, Cruces Hospital, Barakaldo-Bilbao, Spain, ²Hematology, Cruces Hospital, Barakaldo-Bilbao, Spain, ³Immunology Laboratory, La Paz Hospital, Madrid, Spain, ⁴Pediatric Intensive Care Unit, Cruces Hospital, Barakaldo-Bilbao, Spain

11% of children with aHUS belong to DEAP-HUS subgroup; defined by complement (C′) factor H (CFH) acquired dysfunction secondary to CFH-autoantibodies (AutoAb). Genetic HUS susceptibility in most patients relies on CHF related proteins 1&3 (CFHR1&CFHR3) genes deletion. Early recognition of this autoimmune mechanism is crucial as plasma exchange (PEX) and immunosuppressive (IS) treatment achieve remission and therefore, prevent disease progression to renal failure.

Case report: 7 y girl admitted for D-HUS. FHx & PHx were negative for HUS or consanguinity. Lab data revealed microangiopathic hemolytic anemia (Hg 7.9 g/dl, Hct 22.4%, LDH 4401 U/L haptoglobin <0.0775 g/L, 2% schistocytes, platelets 49.000/103), and renal failure (urea 347 mg/dL, Cr 5.8 mg/dL). She recovered spontaneously (urea 19 mg/dL, Cr 0.79 mg/dL, platelets 200.000/103), but suffered a severe relapse 2 weeks later. C3c was low (46 mg/dL; normal 77–210) meaning increased C′alternative pathway hemolytic activity (53%). CFH deficiency (6.8 mg/dL; normal 12–56) secondary to CFH-autoAb (28160 U/mL) was diagnosed, and CFHR1 & CFHR3 genes deletion observed. CFI and MCP levels were normal, without CFH, CFI or MCP genes mutations. Repeated PEX, prednisone and Cyclophosphamide leaded to progressive CFH-autoAb disappearance, C3c and CFH normalization as follows: day2 CFH-autoAb 13376 U/mL, C3c 62 mg/dL, CFH 5 mg/dL; day5 CFH-autoAb 956 U/mL, C3c 63 mg/dL, CFH 11 mg/dL, day7 CFH-autoAb 650 U/mL, C3c 76 mg/dL, CFH 6.4 mg/dL, day28 CFH-autoAb 0 U/mL, C3c 94 mg/dL, CFH 31 mg/dL, and HUS remission. Hemodialysis (x3) was needed too. Two months later CFH-autoAb continue negative despite progressive PEX reduction, and IS tapering, with full renal function recovery.

Comment: Early DEAP-HUS diagnosis supports PEX, and IS therapy to remove and suppress CFH-autoAb synthesis, and improves outcome.

PS2-FRI-462

Clinical and radiological course of simple renal cysts in children

M. Aguirre¹, J. Mateos², C. Abarrategui³, J. López-Bayón⁴, M. López-Trascasa³, G. Ariceta*¹

¹Dokuz Eylul University Medical Faculty Department of Pediatrics, Izmir, Turkey

Aim: We aimed to evaluate the clinical and radiological course of simple renal cysts that are rarely seen in children.

Patients and methods: Hospital files of the children with simple renal cysts were evaluated retrospectively for age at diagnosis, presenting complaint, follow-up period, complications and change in the cyst diameter during follow-up.

Results: Simple renal cyst was detected in 9 (6 male) patients. Mean age at diagnosis was 73 ± 42 (14–144) months and mean follow-up period of the 6 patients with long follow-up was 39 ± 18 (18–58) months. Seven patients were diagnosed incidentally during ultrasonographic evaluation for other medical problems (obesity 2, urinary tract infection 2, voiding symptom 2 and glomerulonephritis 1). Two patients with large cysts had symptoms related to cyst (abdominal pain and abdominal mass + hematuria). Most (n = 7) of the cysts were in right kidney, usually in the lower pole (n = 4). Mean cyst diameter was 25.0 ± 29.7 and 37.4 ± 59.1 mm at diagnosis and at last visit, respectively. Cyst size increased during follow-up in four patients (37.3 ± 42.1 vs 58.5 ± 74.6 mm). One patient was undergone nephrectomy due to rapid increase in cyst diameter (170 mm), renal artery/vein compression and massive hematuria.

Conclusion: Simple renal cysts are rarely seen in children and usually diagnosed incidentally during ultrasonographic evaluation for other reasons. Regular radiological follow-up is important as these cysts may increase in size and become complicated.

PS2-FRI-463

Eculizumab pharmacokinetics and efficacy in a newborn with aHUS: an option in no-candidates to plasmaexchange

M. Aguirre¹, B. Arrizabalaga², C. Abarrategui³, E. Morteruel⁴, M. López-Trascasa³, R. Areses⁵, M.J. Quintela¹, G. Ariceta*¹

¹Pediatric Nephrology, Cruces Hospital, Barakaldo-Bilbao, Spain, ²Hematology, Cruces Hospital, Barakaldo-Bilbao, Spain, ³Immunology Lab, La Paz Hospital, Madrid, Spain, ⁴Pediatric Intensive Care Unit, Cruces Hospital, Barakaldo-Bilbao, Spain, ⁵Pediatric Nephrology, Donostia Hospital, San Sebastian, Spain

Eculizumab is effective in aHUS caused by increased C′alternative pathway activity. It inhibits C5a generation & C5b-C9 complex formation. Few data are available in very small infants.

Case report: 28 day old infant of 3.6 Kg admitted with D-HUS (Hgb 9.2 g/dL, Hct 25.2%, platelets 32 × 109/L, schistocytes 6%, LDH 1429 U/L, haptoglobin <0.07/dL) and renal failure, though repeated plasma infusions (PI). Normal C′ levels were found but meaningless after PI. Homocysteine, methylmalonic acid, and ADAMTS13 levels were normal too. Despite large PI volume, patient severely deteriorated, with generalized disease expression -intestinal ischemia and perforation, skin necrosis-, and continuous hemolytic activity. PEX was attempted but not tolerated, and CVVHD initiated. After 5 days without PI, low C3 (36 mg/dL), increased hemolytic activity, but normal CFH (23 mg/dL), CFI (65%), MCP (94%) were demonstrated. No CFH antibodies or genes mutations were found. IV Eculizumab (300 mg) was initiated, achieving disease remission in 36 hours, diuresis recovery, CVVH removal in 4 days, and gradual renal function normalization (Cr 0.4 mg/dL). However, subsequent lower eculizumab dose (180 mg) resulted in low drug PK value (19.1 ug/mL, target >35), SC5b-9 elevation (from 39.6 to 181.4 ng/mL), and thrombocytopenia (33.000/103). Remarkably, additional 300 mg Eculizumab restored PK value (509 ug/mL), and got C′inhibition (SC5b-9 60 ng/mL) in hours without apparent renal impairment. Nowadays the disease is under remission by 300 mg Eculizumab TIW, patient has normal GFR (Cr 0.3 mg/dL) but proteinuria (Uprot/Cr 1.4 mg/mg), without side-effects.

Comment: Eculizumab is very effective in achieving and maintaining aHUS remission but pharmacokinetic studies are needed in infants and children.

PS2-FRI-473

Arterial stiffness does not increased in teens with early uncomplicated insulin-dependent diabetes mellitus

M. C. Yu* ¹, F. Li¹, F. S. Lo¹, M. K. Yu¹

¹Department of Pediatric nephrology, Chang Gung Children’s Hospital, Lin-Kou Medical Centre, Taiwan

Objective: Patients with insulin-dependent diabetes mellitus (IDDM) are at an increased risk of cardiovascular mortality. Assessment of pulse wave velocity (PWV) is a useful, noninvasive approach to evaluate the severity of arterial stiffness in patients. Changes in PWV could be an early sign of vascular dysfunction. Studies comparing arterial stiffness between patients with IDDM and nondiabetic controls have provided controversial findings. Thus, we investigated and compared brachial-ankle PWV (ba-PWV) between teens with uncomplicated IDDM and matched healthy controls.

Research design and methods: The ba-PWV was measured with an automatic device (VP1000/2000, Colin, Co. Ltd., Japan). Heart rate (HR), body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and ankle-brachial index (ABI = SBP in the ankle/ SBP in the brachial artery) were recorded simultaneously. The ba-PWV was calculated as the ratio of the distance between the brachial and the tibial arteries to the transit time between them.

Results: There was no significant difference between the IDDM teens (n = 87; 51 boys and 36 girls) and the control subjects (n = 21; 13 boys and 8 girls) with respect to the following parameters (data expressed as mean (SD)): age (IDDM teens: 14.1 (2.6) years with diabetes duration 62 (37) months ; control subjects: 13.5 (2.2) years. P = 0.3), BMI (IDDM teens: 20.2 (3.4) kg/m2 ; control subjects: 20.8 (4.7) kg/m2. P = 0.5), SBP (IDDM teens: 111 (11) mmHg ; control subjects: 111 (10) mmHg. P = 0.9), DBP (IDDM teens: 60(8) mmHg ; control subjects: 59(5) mmHg. P = 0.7), ABI (IDDM teens: 1.02 (0.09); control subjects: 1.01 (0.07). P = 0.7) and ba-PWV (IDDM teens: 1020 (154) cm/s ; control subjects: 967 (86) cm/s. P = 0.1). However, owing to the small size of the control group, these results may be inconclusive.

Conclusions: Our data shows that ba-PWV did not increase in teens with uncomplicated IDDM when compared with that in the healthy controls. However, the possibility of early regional atherosclerotic changes or an eventual increase in ba-PWV related to the duration of diabetes can not be excluded.

PS2-FRI-474

Determination of the renal concentration mechanism following desmopressin administration in healthy humans

M. Faerch* ¹, M. K. Schrøder¹, B. T. Mahler¹, K. Kamperis¹, S. Rittig¹

¹Pediatric Research Laboratory, Aarhus University Hospital, Skejby, Denmark

Introduction and objectives: Desmopressin (dDAVP) is an arginine vasopressin (AVP) analogue used for treatment in neurogenic diabetes insipidus (DI), and enuresis nocturna. Further dDAVP is used in differential diagnosis of polyuric disorders. AVP can be used to evaluate renal sensitivity, however, it exerts its effects not only through the vasopressin V2 receptors (V2Rs) in the kidneys, but also on receptors in the peripheral vasculature, the liver and the brain with the possibility of serious adverse affects. dDAVP almost exclusively affects the V2Rs in the kidney collecting ducts, but there is no commercially available assays for measurement of plasma levels. Determining plasma levels is essential when evaluating renal sensitivity to the hormone. We developed a specific radioimmunoassay (RIA) for measurement of dDAVP in plasma in order to anticipate the relationship between plasma dDAVP and urine osmolality, as well as, illustrating the correlation between time of infusion and plasma dDAVP and urine osmolality.

Methods: The RIA was based on a well established assay for measurements of AVP. 4 healthy females and 10 healthy males were enrolled. All obtained day- and nighttime continence at the expected age, was at least Tanner stage IV, and had residual urine <20 ml. Admissions comprised of urine collections and blood sampling. Sodium and water intake was standardized. 0.03 μg/kg desmopressin was administered intravenously. Subjects were discharged when urine osmolality fell below 300 mosm/kg.

Results: Urine osmolality varied greatly between individuals. Plasma dDAVP levels increased in response to intravenous infusion of dDAVP, but decreased rapidly. The increment in urine osmolality continued despite of the decrease in plasma dDAVP. Conclusions: The results presented in this study suggest that renal sensitivity can be determined when measured at 120 minutes subsequent to the infusion of dDAVP. This makes the test valuable in a clinical setting, and makes AVP infusion obsolete.

PS2-FRI-475

Complement blockade by eculizumab: new therapeutic option for shiga-toxin associated hemolytic uremic syndrome?

M. Malina* ^1,2, M. Kirschfink⁴, T. Boppel³, V. Fremeaux-Bacchⁱ⁵, F. Schaefer¹

¹Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany, ²Pediatric dpt., Charles University in Prague—2nd Faculty of Medicine, Prague, Czech Republic, ³Department of Neuroradiology, University of Heidelberg, Germany, ⁴Department of Immunology, University of Heidelberg, Germany, ⁵Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges-Pompidou, Service d’Immunologie Biologique, Paris, France

Background: Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy that occurs either secondary to shiga-toxin (STX) producing E. coli infection or as an atypical form associated with genetic abnormalities in complement regulators. Inhibition of terminal complement complex formation by the monoclonal C5 antibody eculizumab has recently shown efficacy in atypical HUS1.

Case: We report on a 3-year-old girl with shigatoxin-associated HUS following infection with E. coli O157. Anuria rapidly developed and daily hemodialysis (HD) was initiated. Since decreased C3 and elevated C3d serum concentrations suggested complement activation, plasma exchanges (PE) were performed with each HD. After 3 days of persistent hemolysis, anuria and daily HD/PE, a short-lasting episode of impaired motor coordination and altered consciousness occurred. Two days later, she developed impaired eye movements, blurred speech and soon thereafter left-sided hemiplegia accompanied by somnolence progressing to a comatose state. In view of the complement activation and progressive central nervous system involvement, the decision was made to treat the patient with eculizumab. The girl’s neurological condition improved dramatically within few hours following the first infusion. She largely regained consciousness, motor and speech control within 48 hours. Urine production started within 24 hours and dialysis was discontinued three days later. Serum C3 and C3d normalized. Nine days after the first eculizumab administration the patient was discharged with completely normalized neurological status. Renal function fully recovered within 2 weeks, with slight residual proteinuria and borderline hypertension. Clinical and biochemical remission has persisted 6 months post-event. Mutation screening of the complement regulatory protein genes (CFH, CFI, MCP, C3, CFB, and THBD) did not reveal any abnormalities.

Conclusion: The successful administration of eculizumab in our case defines a new, potentially curative therapeutic option for complicated classical HUS.

PS2-FRI-476

Peripheral gangrenes in children with atypical hemolytic uremic syndrome

M. Malina* ^1,2, A. Gulati³, M. A. Majid⁴, A. Bagga³, F. Schaefer¹

¹Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany, ²Pediatric dpt., Charles University in Prague—2nd Faculty of Medicine, Czech Republic, ³Pediatric dpt., All India Institute of Medical Sciences,New Delhi, India, ⁴Department of Pediatrics, Pediatric Nephrology Unit, Dubai, UAE

Background: aHUS is a thrombotic microangiopathy with severe clinical manifestation, frequent recurrence and poor long-term prognosis. It is usually caused by abnormalities complement cascade regulators.

Cases: We report two cases of children affected by a catastrophic extrarenal complication of aHUS. A 4-year-old Indian girl developed gangrene of the finger tips two days after initial presentation of aHUS. Factor H auto-antibodies were identified. Renal function continued to decline despite daily sessions of FFP exchanges and she was started on peritoneal dialysis 5 days after admission. The distal tips of the left hand remained gangrenous with a line of demarcation. Three weeks later she did not return for follow-up and died at home because of non-infectious dialysis related complications. An Arabic girl first presented with aHUS in the second month of life. The disorder was partially responsive to plasma infusions, but multiple recurrences led to ESRD and PD was started at age 4 months. An activating C3 mutation was found as the cause of disease. At the age of 9 months, she suddenly developed ischemic changes in fingers of both hands and several toes. Because the lesions progressed and several finger tips became gangrenous despite immediate plasma exchange therapy, emergency complement blocking therapy with the monoclonal C5 antibody eculizumab (300 mg) was started. Immediately after eculizumab administration all non-necrotic digits regained perfusion. The three fingers with already established gangrene healed with loss of the end phalanges. The patient was continued on three-weekly Eculizumab maintenance infusions. aHUS activity has subsided completely, and some late recovery of kidney function has occurred within the past 10 months with an increase in measured GFR from 1 to 6 ml/min/1.73 m².

Conclusion: In rare cases aHUS can present by thrombotic macroangiopathy of small peripheral arteries. Eculizumab effectively prevents or interrupts the course of this complication.

PS2-FRI-491

Approach of pediatric residents to the initial work-up of asymptomatic proteinuria

O. Akchurin* ^1,2, J. Springate^1,2

¹The State University of New-York at Buffalo, USA, ²The Women & Children’s Hospital of Buffalo, USA

Background: There is a lack of evidence in the literature regarding the standards of initial work-up of asymptomatic pediatric proteinuria. Determination of urine protein to creatinine ratio (Pr/Cr ratio) is an exception and is recommended by current guidelines and supported by some research evidence. The goal of this study was to investigate the knowledge of pediatric residents of the initial proteinuria work-up.

Methods: The study was carried out using an anonymous on-line survey. Pediatric residents from different programs across the United States were offered a number of laboraratory and imaging tests and were asked to choose 1) the test(s) that they will always order in any case of asymptomatic proteinuria diagnosed by a dipstick and also 2) tests that they would consider to order depending on the case.

Results: A total number of 91 residents have responded to the survey. The leading tests that respondents chose as standard were urinalysis with microscopy (53.2% respondents) and BMP (41.8%). The leading \“optional\” tests were renal ultrasound (35.4%) and serum C3/C4 complement levels (34.2%). Pr/Cr ratio in the first morning sample was chosen by only 25.3% respondents, which is significantly different from top 2 choices (p < 0.01 and p < 0.05). There were no statistically significant differences in the frequency of choosing Pr/Cr ratio among the residents of different levels of training.

Conclusion: Our data showed that further educational and research efforts are required to improve and uniform approach of pediatric residents to the proteinuria work-up. Particularly, significance of Pr/Cr ratio determination in the work-up of pediatric proteinuria and adherence to the current guidelines should be emphasized during pediatric residency training.

PS2-FRI-493

Outcome of Henoch Schönlein purpura 8 years after the treatment with placebo or prednisone at disease onset

O. Jauhola* ¹, J. Ronkainen², O. Koskimies³, M. Ala-Houhala⁴, P. Arikoski⁵, T. Hölttä³, T. Jahnukainen³, J. Rajantie⁶, T. Örmälä⁷, M. Nuutinen¹

¹Oulu University Hospital, Department of Pediatrics, Oulu, Finland, ²Oulu City Health Care Center, Oulu, Finland, ³Helsinki University, Hospital for Children and Adolescents, ⁴Tampere University Hospital, Department of Pediatrics, Tampere, Finland, ⁵Kuopio University Hospital, Department of Pediatrics, Kuopio, Finland, ⁶Helsinki University Central Hospital, Jorvi Hospital, Department of Pediatrics, Helsinki, Finland, ⁷Hyvinkää Hospital, Department of Pediatrics, Hyvinkää, Finland

Objectives: To assess 8-year outcome of unselected HSP patients and the long-term effect of prednisone compared to placebo.

Methods: 134 of the 171 (78%) of patients who had attended randomized prednisone versus placebo study were screened mean 7.5 years (4.6–11.1 years) later by assaying erythrocytes and U-Protein/creatinine ratio from spot urine sample, measuring blood pressure and using health questionnaire. Patients having abnormal results were invited for physician’s examination.

Results: Hematuria was recorded in 8 patients, proteinuria in 2 patients and both hematuria and proteinuria in 1 patient. However, the renal findings were transient in all except for one patient who had persistent proteinuria and was therefore referred for kidney biopsy. Elevated blood pressure was recorded in 8 patients, presenting with hematuria in 1 patient. Recurrence of purpura after the 6 month study follow-up was self-reported in 11 patients, of which in 3 the first relapse appeared after 1–4 years. In 2 patients the purpura symptoms appeared frequently during 9 years after initial disease onset provoked by respiratory infections and physical or emotional stress. In the other of these patients, transient hematuria accompanied the skin symptoms. Patients with nephritis at the acute phase of disease had more often elevated blood pressure and urine abnormalities in the screening (p = 0.003). There were no differences between patients receiving prednisone or placebo at early phase.

Conclusions: HSP has good prognosis in unselected patients. Skin relapses may occur years after initial disease onset. Early prednisone treatment does not affect the long-term outcome and should not be routinely used.

Reference: Ronkainen et al: Early prednisone therapy in Henoch-Schönlein purpura: a randomized, double-blind, placebo-controlled trial. J Pediatr 149: 241–247, 2006.

PS2-FRI-507

Rituximab in steroid dependent idiopathic nephrotic syndrome in childhood—follow up after CD19 recovery

A. L. Sellier-Leclerc* ^1,2, V. Baudouin¹, T. Kwon¹, M. A. Macher¹, V. Guérin³, H. Lapillonne^4,5, G. Deschênes^1,6, T. Ulinski^2,5

¹Department of Pediatric Nephrology, Robert Debré Hospital, AP-HP, Paris, France, ²Department of Pediatric Nephrology, Armand Trousseau Hospital, AP-HP, Paris, France, ³Laboratory of Immunology, Robert Debré Hospital, AP-HP, Paris, France, ⁴Laboratory of Hematology, Armand Trousseau Hospital, AP-HP, Paris, France, ⁵University Pierre et Marie Curie, Paris 6, France, ⁶University Denis Diderot, Paris 7, France

Rituximab (RTX) is a new treatment strategy in high degree steroid dependent idiopathic nephrotic syndrome (SDNS) in childhood since 2006, but longterm observational studies are still lacking. Thirty patients (9 girls) with severe SDNS and previously treated with immunosuppressive drugs, mostly calcineurin inhibitors, were treated with RTX and included in this single center study. Despite absence of pathophysiological evidence, CD19 depletion was shown to be correlated with remission in the absence of other immunosuppressive drugs but nephrotic syndrome relapse occurred frequently a few months after CD19 recovery. Therefore, we proposed a prolonged B cell depletion period of 15 months.

Patient age at first RTX infusion was 9.5 ± 0.83 years. Minimal follow-up after initial CD19 depletion was 24 months and CD19 depletion period was 20.5 ± 0.92 months. Six patients had nephrotic syndrome relapses during the RTX treatment period at the time of an intermittent CD19 recovery, which occurred before a new RTX infusion could be performed, and one patient relapsed under CD19 depletion. The risk for these patients to relapse after the RTX treatment period was higher than in those without intermittent relapses. 19/30 patients did not relapse after full CD19 recovery over a follow up of 14.4 ± 1.5 months. The remaining 37% relapsed 4.8 ± 0.96 months after full CD19 recovery. Patients younger than 10 years had a tendency to higher relapse risk than patients older than 13 years. Steroid and immunosuppressive treatment could be discontinued in all patients during CD19 depletion and was re-introduced in two after CD19 recovery. Fourteen patients had mostly benign and transitory side effects, which did not require RTX discontinuation. In conclusion, RTX treatment with a 15-month CD19 depletion period induced long-term remission after full CD 19 recovery in almost two third of patients.

PS2-FRI-508

Etiology of nephrocalcinosis in children: a retrospective study

C. S. Dogan¹, A. Uslu Gökcoglu¹, E. Çomak¹, A. E. Kuybulu¹, E. Alimoglu², M. Koyun¹, S. Akman* ¹

¹Akdeniz University Medical Faculty, Department of Pediatrics, Division of Pediatric Nephrology, Antalya, Turkey, ²Akdeniz University Medical Faculty, Department of Radiology, Antalya, Turkey

Aim: The aim of this study was to analyze the clinical presentation and the etiology of nephrocalcinosis (NC) in children.

Methods: The children who were diagnosed with bilateral NC between November 1991–January 2011 at our department were studied retrospectively. The diagnosis of NC was made by ultrasonography. The records of patients were evaluated for sex, height, weight, age at diagnosis, conditions leading to NC, signs and symptoms at presentation, follow-up-time, prognosis and laboratory findings including urinary calcium excretion, serum calcium, magnesium and creatinine levels.

Results: Twenty eight patients, 14 boys (50%), with a mean age at diagnosis of 21.6 ± 31.8 months (2–159 mo) and median follow-up time of 46.5 (2–233) months were included. The most common condition leading to NC was distal renal tubular acidosis (dRTA) in 9 patients (32.1%), followed by Bartter syndrome in 5 (17.9%), vitamin D intoxication in 3 (10.7%), idiopathic hypercalciuria and hyperoxaluria in 2 (7.1%) of each, and autosomal recessive polycystic kidney disease (ARPKD) in 1 (3.6%) patients; the etiology could not be found in 6 (21.4%). The most common signs or symptoms at presentation were polyuria-polydipsia in 7(25%), growth retardation and psychomotor delay in 5 (17.9%), urinary tract infection, vomiting and dehydration in 4(14.3%) of each. At follow-up, chronic renal insufficiency developed in 4(14.3%) all of patients (two with Bartter’s Syndrome, one with dRTA and one with ARPKD).

Conclusion: Children with nephrocalcinosis, which may be associated with severe renal disorders, may present with various sign and symptoms. Early determination of NC may provide early diagnosis and treatment of relevant renal diseases.

PS2-FRI-510

VTEC associated Hemolytic Uremic Syndrome in Scottish children

S. Bhojani* ¹, K. G. J. Pollock², A. Balfour¹, T. J. Beattie¹

¹Royal Hospital for Sick Children, Glasgow, UK, ²Health Protection Scotland, Glasgow, UK

Objective: Hemolytic Uremic Syndrome (HUS) is commonly associated with verotoxin-producing E. coli(VTEC). An ongoing Scottish surveillance programme indicates EcoliO157 is the commonest organism. We reviewed all 13 patients admitted with HUS to the Scottish tertiary referral centre (Royal Hospital for Sick Children, Glasgow) in 2010.

Methods: We reviewed the clinical presentation, hospital progress and renal replacement therapy (RRT) requirement of all 13 cases. We divided the cohort into three groups: Group A (6 patients with E.coliO26 as the associated VTEC), Group B (5 patients with E.coliO157) and Group C (2 patients with E.coliO71 and unidentified VTEC).

Results: Group A: Age 3.2 ± 1.7 years. Male:Female ratio 1:1. 4/6 had bloody diarrhoea(BD) and 2/6 presented with fever. 3/6 had traveled abroad. 4/6 required RRT. 3/6 patients had CNS and 1/6 had cardiac involvement. 2/6 had diabetes, 3/6 hypertension and 3/6 PICU admission. Hospital stay ranged from 4–40 days.

Group B: Age 3.5 ± 2.3 years. Male:Female ratio 2:3. 4/5 had BD and 2/5 were febrile. 3/5 required RRT. None had diabetes, hypertension, CNS or cardiac involvement. No PICU admissions. Hospital stay ranged from 7–10 days.

Group C: Age 10.2 ± 5.7 years. Both females. Neither patient had BD and one had fever. No CNS/cardiac involvement or need for PICU admission or RRT. Hospital stay ranged from 4–12 days. No patient in the cohort required RRT on discharge.

Conclusion: 62% of the cases had non-O157 E. coli associated HUS. Patients with E.coliO26 associated HUS had a prolonged and complicated clinical course with CNS and cardiac involvement and an increased PICU admission rate. This study suggests a changing epidemiology of VTEC associated HUS in Scotland.

PS2-FRI-513

Renal tubular function in children with primary nocturnal enuresis

S. Kalman* ¹, O. Sakallioglu¹, V. Kesik¹

¹Gulhane Military Medical Academy Deparment of Pediatric Nephrology, Ankara, Turkey

Background: An unique factor is not available in the etiology of primary nocturnal enuresis (PNE). The effects of genetical, hormonal and psychological factors, sleep disorders, and bladder dysfunction have been claimed. Another efficient factor is the arisen of urine volume at night up to the compromised circadian rthym of antidiuretic hormone (ADH).

Aim: To investigate the ADH effect via fractional excretion of sodium(FeNa) and potassium (FeK),tubular phosphor reabsorption (TRP) and urine density in PNE.

Patients and methods: 40 patients (18 female/22 male-mean age of 7.8 ± 2.9 years) with PNE were included in study. Urine density, FeNa, FeK and TRP were analyzed at daytimed and nighttimed urine. The cases with mental retardation, neurological disorders, metabolic diseases, psychiatric abnormality (attention deficit/hyperactivity syndrome) and urinary tract disorders were excluded.

Results: As the mean urine density was 1020.12 ± 7.38 at daytime, the mean density was 1013.20 ± 7.11 (p < 0.05) at nighttime. The mean FeNa (0.50 ± 0.48 vs 0.38 ± 0.33) the mean FeK (2.78 ± 1.04 vs 2.76 ± 1.52) and the TRP% (88.5 ± 2.4 vs 86.7 ± 2.8) at daytime and night were not significantly differed (p > 0.05).

Conclusion: Though the recent reports about the comparable ADH excretions between the children with PNE and controls, the urine density of enuretics at night was lessened in our study. However, there was no difference in the face of FeNa, FeK and TRP. It was convinced that the more extended studies are essential at the evaluation of renal tubular functions in PNE.

PS2-FRI-518

Hypomagnesemia-hypercalciuria-nephrocalcinosis and ocular findings: a new claudin-19 mutation

Z. Ekinci* ¹, Ö. Kayabey², M. Konrad³

¹Kocaeli University School of Medicine, Department of Pediatric Nephrology, Kocaeli, Turkey, ²Kocaeli University School of Medicine, Department of Pediatrics, Kocaeli, Turkey, ³University Children’s Hospital Muenster, Department of General Pediatrics, Pediatric Nephrology, Muenster, Germany

Objectives: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal resessive syndrome which affects the tight junction proteins’ claudins-16 and 19 in the thick ascending limb. More than 45 caludin-16 and four claudin-19 mutations have been reported. Claudins are especially important for the regulation of paracellular ion permeability. The typical clinical presentation of FHHNC is disturbances in magnesium and calcium homeostasis, recurrent urinary tract infections, polyuria, polydipsia, nephrocalcinosis and hypercalciuria. In patients with claudin-19 mutations additional symptoms visiual impairment and other ophtalmologic findings are expected.

Case report: In this report we are going to present a 7-year-old girl who presented with polyuria and polydipsia. She was the daughter of consanguineous parents with a history of neonatal hypomagnesemic convulsion. On physical examination bilateral horizontal nistagmus was detected. Ocular examination revealed retinitis pigmentosa and severe myopia. Laboratory examination revealed urine pH: 7, blood pH: 7.38, HCO₃:19.7 mEq/l, serum creatinine: 0.8 mg/dl, serum magnesium: 1.2 mg/dl, urine calcium: 12.2 mg/kg/day, urine magnesium: 3.37 mmol /day (<0.46 mmol/day), PTH: 466.7 pg/ml (15–65 pg/ml). Clinical diagnosis of FHHNC caused possibly by claudin-19 mutation was decided with the symptoms polyuria, hypomagnesaemia, hypercalciuria, nephrocalcinosis and ocular findings. DNA analysis revealed a novel homozygous nonsense mutation (W169X). This mutation results in a preterminal stop codon leading to a shortened claudin-19 protein which lacks the C-terminal end.

Conclusion: As a conclusion, in a patient with consanguineous parents, history of hypomagnesaemic convulsion and undisturbed organization and development of retina, diagnosis of FHHNC caused by claudin-19 mutation should be thought.

PS2-FRI-530

Juvenile form of Panonian-Balkan endemic nephropathy (PBEN)

Z. Bozic¹, Z. Puretic* ², M. Belicza³, D. Tomas³

¹Private urologic practice, Zagreb, Croatia, ²University Hospital Centre Zagreb, Division of Nephrology, Hypertension and Dialysis, Zagreb, Croatia, ³Department of Pathology, Sisters of Mercy University Hospital, Zagreb, Croatia

Objectives and study: The aim was to research the occurrence of juvenile PBEN in Croatia from 1970–2010. Frequency of PBEN patients up to 20 years of age during the 1950s was 8,3% in Romania, and 1,4% in Croatia.

Methods: The research included 2 female and 2 male patients at the age of 10–15, from the affected households of Croatian endemic focuses. They were examined according to basic epidemiological parameters, as well as the results of clinical diagnostic procedure and treatment. PBEN was confirmed by histopathological examination.

Results: In 3 cases PBEN appeared intercurrently with acute respiratory infection and had extremely progressive course. In the fourth case it was discovered by preventive surveillance and had slower development. Progressive renal failure lead to death in one case during the preparation for haemodialysis, in the second one during the first haemodialysis, while the third case underwent haemodialysis on time and later had renal transplantation. The fourth patient was also treated by haemodialysis and renal transplantation. Althought residential history, clinical examination, and considerably diminished renal size indicated PBEN, the discharge diagnosis in only one patient corroborated real nature of the disease. Histopathological diagnosis (HPD) was performed in 2 cases after autopsy, and in 2 cases after renal biopsy. In all cases histological findings showed several fetal-like glomeruli, glomerular hyalinosis, interstitial fibrosis, tubular atrophy, and hiperplastic thickenning of intrarenal arteries, which corresponds to the description of «Hrisoho\’s primary small kidney». Primary HPD was PBEN in one case, while in the others it was glomerulonephritis and chronic pyelonephritis. Subsequent expertise established that all kidneys showed typical histological pattern of the juvenile PBEN, which differs from adult form of the disease.

Conclusion: The suspicion that clinically unique juvenile PBEN really exists is firmly established, however, it requires further research.

PS2-FRI-531

Cyclosporine responsiveness in Denysh-Drash syndrome

A. Wasilewska* ¹, E. Kuroczycka-Saniutycz¹, W. Zoch-Zwierz¹, K. Taranta-Janusz¹

¹Department of Paediatrics and Nephrology, Medical University of Bialystok, Poland

Denys-Drash syndrome (DDS) is characterized by progressive glomerulopathy caused by diffuse mesangial sclerosis (DMS), genitourinary defects and a higher risk of developing Wilms’ tumor. It is commonly assumed that the DMS is unresponsive to any medications. DDS is mainly caused by mutations in the WT1 gene, which encodes a transcription factor involved in kidney and gonadal development.

Here we present the patient with Denys-Drash syndrome, in whom the cyclosporine A (CsA) was found to induce total remission of proteinuria. The girl in this report had early-onset steroid resistant nephrotic syndrome secondary to DMS, what was confirmed in kidney biopsy. Genetic studies showed mutations in intron 9 of WT1 gene c.1180 C > T (mutational analysis was performed thank to Prof. Friedhelm Hildebrandt; University of Michigan). This is the most common mutation found in DDS. The full diagnosis was done in the 8th month of life. The girl fulfilled the criteria of nephrotic syndrome definition. No reaction for initial prednisone treatment was found. In this situation CsA therapy was started with a significant reduction of proteinuria and remission of nephrotic syndrome. Three months following a dose of 5–6 mg/kg/24 hours a complete remission of proteinuria was observed. After the dose reduction the proteinuria recurred.

Cyclosporine A (CsA) has been used in the treatment of idiopathic syndrome for 20 years. The mechanism of CsA action in minimal change disease was the inhibition of NFAT signalling in T lymphocytes. However the therapeutic effect of CsA in genetic nephrotic syndrome is probably related to a direct influence of CsA on podocytes.

Our observation and observations of other authors confirm the beneficial effect of CsA treatment in genetic nephrotic syndrome; however the potential nephrotoxicity of this drug will probably not allow the long-term use. Understanding the regulation of podocyte actin dynamics in glomerular diseases and the role of calcineurin-cathepsin L in this process may be the starting point for developing new podocyte-protective drugs.

PS2-FRI-534

Urinary OPN excretion in children with glomerular proteinuria

A. Wasilewska* ¹, K. Taranta – Janusz¹, E.Kuroczycka – Saniutycz¹, W.Zoch – Zwierz¹, E. Sobiecka¹

¹Department of Paediatrics and Nephrology, Medical University of Bialystok, Bialystok, Poland

THE AIM of the study was to investigate urinary levels and clinical significance of osteopontin (uOPN) in children with different glomerular diseases according to histological diagnosis and degree of proteinuria.

Patients and methods: The examinations were conducted in 3 groups of children: I: 20 children with minimal change disease (MCD) examined twice: A—during proteinuria relapse; B—after proteinuria subsided, group II—17 children with focal segmental glomerulosclerosis (FSGS), III—12 children with IgA nephropathy (IgAN). The control group (C) contained 20 healthy children. OPN was measured in the urine using ELISA commercial available kit (R&D Quantikine) and was expressed in ng/ mg cr.

Results: The median uOPN/ cr. in MCD children in relapse (IA) was median 134.98 ng/ mg cr. and was higher when compared to controls (p < 0.01). In exam IB, when proteinuria subsided, OPN/ cr. increased to median 172.96 ng/ mg cr. and was higher in comparison to healthy subjects (p < 0.01) and MCD children in relapse (p < 0.05). Children from groups II revealed higher uOPN/ cr. levels when compared to groups I, III and C (p < 0.01). UOPN/ cr. positively correlated with protein/ creatinine ratio in all examined groups of children (p < 0.01).

Conclusion: We found significantly higher uOPN/ cr. in all the groups of children with glomerulonephritis. The highest uOPN/ cr. levels were found in patients with FSGS and correlated significantly with both interstitial changes and mesangial expansion found in kidney biopsy.

PS2-FRI-535

Henoch-Schönlein purpura nephritis: future strategy

J.C. Davin* ^1,2,3

¹Pediatric Nephrology Departments, Emma Children’s Hospital-Academic Medical Centre, Amsterdam, The Netherlands, ²University of Amsterdam and Queen Fabiola Academic Children’s Hospital, Amsterdam, The Netherlands, ³Free University of Brussels, Brussels, Belgium

Henoch-Schönlein purpura nephritis (HSPN) is a rare kidney disease leading to chronic kidney disease in a non negligible percentage of patients. Although retrospective studies suggest beneficial effects of some therapies, prospective randomized clinical trials proving treatment efficacy are still lacking. Dilemma of spontaneous recovery even in cases with severe clinical and histological presentation and/ of late evolution to chronic kidney disease in cases with mild initial symptoms renders it difficult for clinicians to expose patients to treatment protocols which are not evidence-based. A better understanding of the pathophysiology of progression to chronic kidney disease in HSP patients could be achieved by designing prospective international multicentre studies looking at determinants of clinical and histopathological evolution as well as possible circulating and urinary markers of progression. Such studies should be supported by a database available on the web and a new histological classification of kidney lesions.

This paper reports clinical, pathological and experimental data to be used for this strategy and to assist clinicians and clinical trial designers to reach therapeutic decisions (JC Davin, CJASN 2011)

PS2-FRI-536

Prophylactic plasmapheresis (PE) and eculizumab (EC) allow long term renal function preservation in FH mutation related atypical haemolytic uremic syndrome (aHUS)

J.C. Davin* ^1,2, J.W. Groothoff¹, F.J. Bemelman,^3,A.H. Bouts¹

¹Pediatric Nephrology, Emma Children’s Hospital/ Academic Medical Centre, Amsterdam Z-O, The Netherlands, ²Pediatric Nephrology, Queen Fabiola Academic Children’s Hospital/ULB, Brussels, Belgium, ³Nephrology, Academic Medical Centre, Amsterdam Z-O, The Netherlands

Background: aHUS with CFH mutation is at 75% risk for ESRF and at 80% risk for renal allograft lost to recurrent disease within 2 years.

Patients:18 y follow-up of 3 sisters (including monozygotic twins) with aHUS and the same CFH mutation. A similar natural evolution and response to treatment would be expected for the three patients, as they all presented with no mutation for other complement factors and the same at risk polymorphisms for CFH and CD46.

Method: Because of immediate ESRF at first aHUS episode and 2Tx lost by recurrence under no or insufficient plasma therapy in the older sister, intensive PE was used at first episode or recurrence: daily sessions until pl.creat normalisation followed by progressive tapering and indefinitely prolongation; in case of Tx: pre-Tx session followed by daily PE for one week, tapered until 1PE/w and indefinitely prolonged.

Results: a/ older sister: after 14 y dialysis and 2 immediate Tx losses by recurrence, successful third Tx (Tx3) despite recurrence at month 8. Severe cerebral artery stenosis present after 12 y dialysis. At month 12 post-Tx3, PE was shift to EC because of severe reactions to plasma. Pl.creat: 125 μmol/L 3 years post Tx3, at 20 y age; b/ twin 1: after 2 years dialysis, successful first Tx (Tx1) despite several CMV infection-associated recurrences. Pl. creat: 150 μmol/L at age 17 y, 8 y after Tx1. c/ twin 2: complete recovery after first episode. Pl.creat. 58 μmol/L at age 17 y, 10 y after first HUS episode. No cerebral artery stenosis demonstrated in both twins after 10 y evolution.

Conclusions: Intensive en prophylactic PE, eventually shifted to EC allows long term preservation of renal function of native kidney and of transplant and might prevent large vessels stenosis in FH mutation-related aHUS.

PS2-FRI-537

The levamisole study in steroid sensitive idiopathic nephrotic syndrome (SSINS): completion is approaching

M.P. Gruppen¹, A.H. Bouts¹, J.C. Davin* ¹

¹Emma Children’s Hospital-Academic Medical Centre of Amsterdam, Amsterdam, The Netherlands

Objectives: To assess the efficacy of one year of alternate day levamisole 2.5 mg/kg in the prevention of relapses and prolonging the time to relapse after cessation of corticosteroids treatment in children with SSINS.

Design: A multi-centre, double-blind, placebo-controlled, randomized clinical trial (RCT) followed by a cohort study, using the infrastructure of the RCT.

Participating countries: Netherlands, Belgium (coordination Dr. T. Schurman), France (coordination Pr Niaudet),Italy (Bambino Gesu Ospedale:Dr L Massela, Pr F Emma),India,(All India Institute:Pr A Bagga),Poland: Pediatric Hospital of Gdanks (Dr. A. Zurowska, Dr. Maternik).

Financial support: ACE Pharmaceuticals (study medication manufacturing and distribution, pharmacokinetics), French Ministry of Health, Dutch Kidney Foundation, Emma Foundation, Dutch Orphan Disease Foundation, Dutch Agis Health Insurance.

Authorizations: 2004: official ESPN study; 2005:Orphan Drug denomination (EMEA),priority for ACE Pharmaceuticals to commercialize levamisol (EMEA),approval of study protocol (EMEA);2006: AMC and national Dutch Medical Ethical Commission;2007: Medical Ethical Commission Bambino Gesu Ospedale, Roma;2009: Belgian, French, Polish, Indian Medical Ethical Commissions.

Inclusion: 100 patients needed; in April 2011: 80 patients already included. Inclusion completion expected end 2011.

Agenda: Temporary conditional registration for human use in 2012, study completion in 2013.

Conclusion: According to results of intermediate analysis, it might be expected that levamisole will be commercialized again for human used, registered for the indication of idiopathic nephrotic syndrome and available in tablets of different dosage adapted to age in a delay of one year.

PS2-FRI-538

Nephrotic syndrome registry: an update

N.W. Rutjes* ¹, A.M. van Meel¹, A.H.M. Bouts¹, M. Charbit², P. Niaudet², J. C. Davin¹

¹Emma Children’s Hospital Academic Medical Center, Amsterdam, The Netherlands, ²Hopital Necker-Enfants Malades, Paris, France

Objectives: In February 2010 a global web-based registry (https://doi.org/www.nsregistry.org) was launched to study children particularly with complicated idiopathic nephrotic syndrome and to provide a framework for the organization and implementation of clinical trials. In addition to a doctor domain, a dedicated patient domain was developed in collaboration with the EURO-WINS working group and NephcEurope, a European patient organization.

Methods: Children aged 0–17 years with idiopathic nephrotic syndrome, complicated by steroid dependence, steroid resistance or frequent relapses were eligible for inclusion in the registry. Through a secured web based registry data collection was initiated in February 2010.

Results: Between February 2010 and March 2011, 14 centers from the Netherlands, Belgium, Germany, Turkey, Russia and India participated in the registration of 232 patients. At inclusion, patients were diagnosed with: minimal change nephrotic syndrome (n = 56), focal segmental glomerulosclerosis (n = 32), inconclusive (n = 7), other (n = 16), unknown (no biopsy performed) / not registered (n = 127). Thirtyone patients were registered with frequent relapses. 16 patients had steroid sensitive nephrotic syndrome, 26 patients were steroid dependent and 16 patients were steroid resistant.

Conclusions: An international registry of children with idiopathic nephrotic syndrome was launched in February 2010. Over 230 patients have been included in the registry and additional data collection is in progress. Currently the first clinical trial is being implemented. (Presented on behalf of the EURO-WINS working group).

PS2-FRI-539

A highthrouput screen for new therapeutic approaches in polycystic kidney disease using a zebrafish model system

M. Schmidts* ^1,2, D. Osborn², P. Beales²

¹Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Germany, ²Molecular Medicine Unit, Institute of Child Health, University College London, UK

Background: (Poly)Cystic kidney disease is a common cause of ESRD and in addition to ADPKD and ARPKD several syndromic diseases such as Meckel-Gruber-Syndrome, Bardet-Biedl-Syndrome and Nephronophthisis/ Joubert-syndrome are associated with cystic kidneys. We postulate that there is a “common end pathway” in all these cystic kidney forms despite the different genetic origin of cysts and by targeting this pathway and therefore therapeutic approaches for one of these disease forms are likely to be useful in other forms as well. Together, these diseases represent a significant health and economic burden and so far, the results of human trials have been rather disappointing despite several promising approaches in animal models leaving a need for new approaches. As many pharmaceutical substances have unknown side effects, substances inhibiting progression of cystic kidney disease might already be on the market unrecognised.

Aim of this study: In this study we use zebrafish as a model for a high-throughput drug screen to identify potential new therapeutic targets in cystic kidney disease using substances already on the market.

Results: We performed a high-throughput screen using a zebrafish gene-knockdown model to test 880 FDA-approved substances for their potential to inhibit pronephric cyst formation and expansion and identified 40 substances of which 39 have not been previously known to inhibit cyst growth in. So far, 20% of these “hits” successfully inhibited cyst growth in a E13.5 metanephric kidney explant model (cysts are induced using 8-Br-cAMP). Their mechanism of action is currently under investigation as well as their effect on kidney cysts in a genetic mammalian model.

Conclusion: Cystic kidney disease is a significant health problem and until today, there is no efficient therapy available. We show that zebrafish models are suitable for high-throughput therapeutic substance screens and we are optimistic that we identified several new therapeutic approaches for polycystic kidney disease.

PS2-FRI-703

NPHP1 homozygous deletion rate in Hungarian children with juvenile nephronophthisis

A. Kerti* ¹, R. Antalfi¹, E. Balogh¹, V. Moriniere², A. Szabó¹, P. Sallay¹, G. Reusz1, S. Saunier², C. Antignac², K. Tory¹

¹Ist Department of Pediatrics, Semmelweis University, Budapest, Hungary, ²INSERM U983, Necker Hospital, University Paris Descartes, Paris, France

Juvenile nephronophthisis (NPH) is responsible for 6–10% of ESRD in childhood. The homozygous deletion of the NPHP1 is responsible for 22–45% of NPH cases, but has not yet been screened in Hungary. Within the cohort of 67 Hungarian children and young adults treated at the Semmelweis University with cystic kidney disease or chronic renal failure without hematuria, proteinuria or urinary tract malformation, 22 patients have been diagnosed as NPH based on clinical symptoms, recessive inheritance and renal morphology. Five of these patients presented with Joubert syndrome (JS) and 1 patient with Senior-Loken syndrome (SLS).

The 22 patients with NPH have been screened for the NPHP1 homozygous deletion by the amplification of exons 7, 19, and introns 2, 18. An extragenic region was amplified as a control. Eight of 22 patients with NPH (36%) have been found to carry NPHP1 homozygous deletion. They have all developed ESRD at the median age of 14 years (range: 13–18). Out of them, 4 patients presented with isolated NPH, 2 patients with JS, 1 with SLS and 1 with NPH and sensorineural hearing impairment. The clinical phenotype was particular in three cases. The retinopathy of the patient with SLS is more severe than expected in patients with NPHP1 mutations; his visual acuity at the age of 29 years is lost one one side and 0,25 on the other. One patient with JS was treated with autism, which is not exceptional in JS, but has not been reported in patients carrying NPHP1 mutations. Finally, one child is treated with sensorineural hearing impairment which is rarely associated to NPH.

The rate of NPHP1 homozygous deletion is similar in Hungary to that in world-wide cohorts. The associated extra-renal symptoms can be more extreme than previously found. This work was supported by Pfizer, TÁMOP-4.2.1/B-09/1/KMR-2010-0001 and Zoltán Magyary fellowship (KT).

PS3-SAT-002

Virtual touch tissue quantification: a new approach to assess renal stiffness in children with vesicoureteral reflux

M. Brugnara¹, M. Zaffanello¹, A. Pedot* ¹, C.Bruno², M. Cecchetto³, A. Boner¹

¹Department of Life and Reproduction Sciences, Division of Pediatrics, University of Verona, Verona, Italy, ²Department of Pathology and Diagnostics, Division of Radiology, University of Verona, Verona, Italy, ³Department of Life and Reproduction Sciences, Division of Pediatric Surgery, University of Verona, Verona, Italy

Vesicoureteral reflux (VUR) is the backup of urine from the bladder into the ureteres frequently associated with congenital or acquired renal damage. The preferred method for visualizing functioning renal parenchyma is 99Tc-DMSA renal scintigraphy. Virtual Touch tissue quantification is an implementation of ultrasound Acoustic Radiation Force Impulse (ARFI) imaging that provides numerical measurements (wave velocity values) of tissue stiffness and the degree of renal fibrosis. The aim of the present preliminary study was to assess renal fibrosis by Virtual Touch tissue quantification in a group of 28 children (17 males, 11 females; age 12 ± 3 years) with primary (n° 18) or secondary VUR (n°10) and history of urinary tract infection. The data obtained in our children were compared with data obtained on 16 healthy children matched for sex and age. The wave velocity values of pathological kidneys were significantly more elevated than values of non affected kidneys (176 ± 45 versus 94 ± 2; p < 0.001). Is very interesting that in cases of unilateral VUR we found wave velocity values, either in the affected kidney (152 ± 40; p < 0.001) or in the controlateral ‘healthy’ kidney (124 ± 16; p < 0.05), higher than values in healthy controls. Moreover we found a significant correlation between the elastosonographic measures and the plasmatic cystatin C (r = 0,434; P < 0.05).

The present preliminary study suggests that Virtual Touch tissue quantification might be an innovative and promising technique to assess tissue stiffness and fibrosis in children with VUR and chronic renal disease. A long-term follow-up might aid to monitor the evolution of renal damage.

PS3-SAT-004

Renovascular hypertension in children—5 years experience

N. Stajic* ¹, J. Putnik¹, A. Paripovic¹, R. Bogdanovic²

¹Institute for Mother and Child Health Care “Dr Vukan Cupic”, Belgrade, Serbia, 2 Institute for Mother and Child Health Care “Dr Vukan Cupic”, Department of Pediatrics, School of Medicine, University of Belgrade, Belgrade, Serbia

Objectives and study: Arterial hypertension (HTN) in children has renovascular origin in 5–25% patients. We present a group of patients with suspected renovascular hypertension.

Methods: From 1.7. 2005. to 1.7.2010. 21 patients with severe HTN, underwent arteriography and selective renal arteriography. In patients where renal arterial stenosis was found, percutaneous transluminal renal angioplasty (PTRA), renal artery stenting or nephrectomy were performed.

Results: 15 male (71%) and 6 female (29%) patients, average age of 11.9 years (3–16) and ABPM load of 85% for systolic and 70% for diastolic pressure. Left ventricular hypertrophy (LVH) had 13 (62%) and retinopathy 9 (43%). Renal artery stenosis was found in 8 (38%). In 3 patients it was bilateral. PTRA was performed in 6 patients, in 1 was unsuccessful. In 2 patients restenosis occurred, in one successful stenting was performed. Revascularization was advocated to another patient with recurrent bilateral restenosis. Three patients hadn’t have restenosis so far. In 6 patients in whom PTRA was done, 4 are off therapy, one has smaller dose of antihypertensive, in one dose is unchanged. Comparing patients with (8) and without (13) stenosis, average load was higher in the first group, for both systolic and diastolic blood pressure - 91% vs. 81% (p < 0.05), and 86% vs. 61%, (p < 0.01) respectively. Other diagnostic procedures showed much lower sensitivity or specificity comparing to arteriography: Doppler sonography 37% and 85%, DMSA 62% and 77%, plasma renine level 75% and 62%, respectively.

Conclusions: Renovascular aetiology is highly represented in patients with severe HTN. Load of diastolic pressure is better indicator of renovascular origin. PTRA was efficient in a half of treated patients. Occurrence of restenosis is not negligible. Renal artery stenting is recommendable only in children who finished their linear growth.

PS3-SAT-010

Circulating endothelial microparticles and development of cardiovascular and kidney disease in obese children

Z. Gündüz¹, İ. Dursun* ¹, S. Tülpar¹, F. Baştuğ¹, A. Baykan², A. Yıkılmaz³, H. Poyrazoğlu¹, T. Patıroğlu⁴, R. Düşünsel¹, L. Akın⁵

¹Erciyes University School of Medicine, Department of Pediatric Nephrology, Kayseri, Turkey, ²Erciyes University School of Medicine, Department of Pediatric Cardiology, Kayseri, Turkey, ³Erciyes University School of Medicine, Department of Radiology, Kayseri, Turkey, ⁴Erciyes University School of Medicine, Department of Pediatric Immunology, Kayseri, Turkey, ⁵Erciyes University School of Medicine, Department of Pediatric Endocrinology, Kayseri, Turkey

Background: As in adults, a higher body mass index, the presence of type 2 diabetes, hypertension and, insulin resistance are strong independent risk factors for both chronic kidney disease and ESRD in the children and adolescent. On the other hand, it is believed that endothelial dysfunction, an early stage of atherogenesis, in obesity begin in early childhood. In this study, we aimed to investigate the relationship between the development of cardiovascular disease and kidney disease with the presence of circulating endothelial microparticles (EMPs).

Methods: This study included 58 obese children (mean-age 11.9 ± 2.1 years) and 26 healthy controls (mean-age 11.7 ± 2.1 years). Body composition was detected by the BIA method and 24 hour ambulatory blood pressure monitoring was carried out. Blood samples were taken after an overnight fast. Plasma creatinine, glucose, lipid profile, C-reactive protein (CRP), serum insulin and erythrocyte sedimentation rate (ESR) were measured. From each children 24-hour urine sample were collected and urinary excretions of albumin and protein were calculated. The carotid artery intima media thickness (cIMT) and kidney dimensions were measured by using high-resolution ultrasound and kidney volume was estimated. Left ventricular mass index (LVMI) was calculated using echocardiographic findings. EMPs were measured by Flow-Cytometry.

Results: Body fat mass, intracellular water ratio, blood pressures, ESR, serum triglyceride and insulin levels, HOMA-IR, LVMI, kidney volume were increased in the children with obesity compared to control. Extracellular water ratio, HDL-cholesterol and cIMT were found to be lower in the obese children. GFR, excretions of albumin and protein, and CRP level were similar in obese children and healthy controls. The level CD144 + EMP in the obese group was significantly higher than those in the control group (p = 0.000).

Conclusion: Our findings show that endothelial damage begins early in the obese children.

PS3-SAT-011

Local audit of the paediatric management of urinary tract infection specifically in relation to imaging outlined in nice clinical guidelines CG54

F. Shakur* ¹, H. Al-Lamee¹, N. Sabir¹, S. Vali¹, M. Zaman¹, B. Conway¹

¹Blackpool Victoria Hospital, Department of paediatrics, Blackpool, United Kingdom

Objectives and study: To identify concordance with the National Institute for Health and Clinical Excellence (NICE) guideline (54) on the management of children with UTI. The objective is to ensure that children are receiving the appropriate investigations, especially in terms of imaging for UTIs as per NICE guidance.

Methods: 124 patients aged one month to 16 years of age were identified by the local Microbiology Department as urine testing positive for a UTI between January-December 2008. Data was collected retrospectively using a pro-forma.

Results: 7/16 patients aged 0–6 months were identified as having an atypical UTI. Of these, 2 received an ultrasound (US). Of the 4 patients with recurrent UTI, 0 received an US within the acute period. No patients received either dimercaptosuccinic acid (DMSA) or Micturating Cysto-urethrogram (MCUG) within 4–6 months. Of the 43 patients aged 3 months to 6 years, 2/8 and 1/8 with an atypical UTI had a DMSA and MCUG scan respectively. 7/7 experiencing recurrent UTIs were correctly given an US. In those over 3 years, 2/20 unnecessarily received MCUG scans.

Conclusions: Clinicians must be educated regarding the correct usage of MCUG and DMSA. Recognition of risk factors predominantly constipation and conditions associated with urinary stasis are often forgotten. NICE does not define an \‘acute infection\’ or a \‘seriously ill\’ child; hence management varies. Introduction of a care pathway for children diagnosed with a UTI will prove useful. A care pathway to be established for all children diagnosed with a UTI including sub headings for risk factors. Education of clinicians—regarding scheduling DMSA even with normal ultrasound and risk factors for UTI.To increase awareness of the management of UTIs in children as outlined by the NICE guidelines.

PS3-SAT-013

Role of P-glycoprotein expression and function in cystinotic proximal tubular cells

K. Peeters* ¹, J. Schoeber¹, M. Wilmer², R. Masereeuw², B. van den Heuvel^1,3, E. Levtchenko¹

¹Pediatric Nephrology, University of Leuven, Belgium, ²Department of Pharmacology, Radboud University Nijmegen Medical Center, The Netherlands, ³Department of Pediatric Nephrology, Radboud University Nijmegen Medical Center, The Netherlands

Background: P-glycoprotein (P-gp), an ATP-dependent cation transporter localized on the apical membrane of proximal tubules, plays a role in the efflux of endogenous waste products and xenobiotics, into urine. Studies in P-gp deficient mice showed proximal tubular dysfunction and ATP deficiency combined with swollen mitochondria, resembling the cystinosis phenotype. We investigated whether P-gp is affected in cystinosis and whether it might contribute to the development of renal Fanconi syndrome in cystinosis.

Methods: We used conditionally immortalized (ci) proximal tubular cells (ciPTEC) obtained from urine from cystinotic patients and controls (Wilmer et al., 2010). P-gp expression in ciPTEC was determined by Western blot and P-gp gene expression by qPCR. P-gp-mediated transport was measured, using the fluorescent P-gp substrate calcein in the presence and absence of the P-gp-inhibitor PSC833.

Results: Additionally, the effect of the cystine depleting drug cysteamine on transport activity was determined by the calcein-assay. The activity of P-pg, in presence or absence of PSC833, in control cells is comparable to the activity in cystinotic cells. Cysteamine depletes cystine accumulation in cystinotic cells and had a stimulatory effect on P-gp activity. PO4 uptake was decreased in cystinotic cells compared to control ciPTEC. The uptake was sodium-dependent and in the majority of the cells and conditions tested, both PSC833 and cysteamine (pre-)incubation resulted in significant decreased uptake of phosphate.

Conclusion: Inhibition of P-gp activity in ciPTEC decreased the uptake of phosphate comparable to the phenotype of P-gp deficient mice and to that of cystinosis patients. Although cysteamine depleted cystine accumulation in cystinotic cells and increased P-gp activity, it inhibited phosphate uptake in ciPTEC. This observation is compatible with persistence of renal Fanconi syndrome in vivo under cysteamine therapy and requires further study.

PS3-SAT-018

Serum fetuin-A and vitamin D in children with mild-severe chronic kidney disease: a cross-sectional study

J. Schaible¹, M. Wigger¹, H. Staude¹, E. Drueckler¹, G. Kundt², D. Haffner¹, D. C. Fischer* ¹

¹Department of Paediatrics, University of Rostock, Rostock, Germany, ²Institute of Medical Informatics and Biometry, University of Rostock, Rostock, Germany

Background: Fetuin-A and vitamin D are significant correlates of cardiovascular morbidity in paediatric CKD patients. It is thus far unknown, whether or not serum fetuin-A is affected by the vitamin D status or treatment with vitamin D preparations in these patients.

Methods: In a cross-sectional study, serum concentrations of fetuin-A, 25-Hydroxyvitamin D3 (25OHD), and 1,25-Dihydroxyvitamin D3 (calcitriol) levels were determined in 112 paediatric patients with mild-severe CKD (stage 1–5), and after renal transplantation. 25OHD supplementation and/or calcitriol treatment were given in 64% of patients.

Results: Fetuin-A levels were clearly reduced in dialysis patients but were comparable to healthy controls in those with moderate CKD and after transplantation. Although 64% and 46% of all patients received 25OHD and/or calcitriol treatment, 48% and 20% of patients were 25OHD and/or calcitriol deficient, respectively. Within the whole patient cohort fetuin-A correlated with serum calcium and time-averaged 25OHD dosage (each p < 0.01), but not with the vitamin D status per se. Multiple regression analysis revealed the need for dialysis treatment and 25OHD dosage as independent predictors of fetuin-A concentrations (model r2 = 0.17). In dialysis patients, fetuin-A was inversely correlated with serum CRP, but positively correlated with time-averaged calcitriol dosage and serum PTH (each p < 0.01).

Conclusions: Fetuin-A levels are clearly reduced in children on dialysis but not in those with moderate CKD and after transplantation. Beside the degree of micro-inflammation, the cumulative intake of 25OHD and calcitriol are significant correlates of fetuin-A in these patients. The impact of vitamin D treatment appears to be at least partly mediated by serum calcium.

PS3-SAT-019

Reduced serum fetuin-A in nephrotic children: a consequence of proteinuria?

J. Schaible¹, M. Wigger¹, H. Staude¹, E. Drueckler¹, G. Kundt², D. Haffner¹, D. C. Fischer* ¹

¹Department of Paediatrics, University of Rostock, Rostock, Germany, ²Institute of Medical Informatics and Biometry, University of Rostock, Rostock, Germany

Background: The extracellular protein fetuin-A is a potent soluble inhibitor of calcifi-cation, and its deficiency has been associated with vascular calcification in dialysis patients. In proteinuric patients, significant urinary losses of fetuin-A might occur re-sulting in reduced serum fetuin A levels.

Methods: In a cross-sectional study, urinary/serum concentrations of fetuin-A were investigated in proteinuric children with glomerular diseases and normal renal func-tion (n = 50) in comparison to healthy controls (n = 246).

Results: Mean fetuin-A serum concentrations were clearly reduced in children with active nephrotic syndrome (0.26 ± 0.15 g/l, p < 0.001), slightly reduced in children with large proteinuria (0.39 ± 0.15 g/l, p < 0.05), and comparable to controls in those with mild proteinuria (0.47 ± 0.15 g/l vs. 0.46 ± 0.12 g/l). Fetuin-A showed a positive corre-lation with serum protein (r = 0.576, p < 0.001), albumin (r = 0.604, p < 0.001), 25-Hydroxyvitamin D3 r = 0.438, p < 0.01), and calcitriol (r = 0.582, p < 0.001), while a nega-tive correlation with proteinuria (r = −0.488, p < 0.005), albuminuria (r = −0.425, p < 0.005), and urinary fetuin-A excretion (r = −0.418, p < 0.01) was seen. However, the relative contribution of fetuin-A to proteinuria was rather small, i.e. urinary fetuin-A and protein concentrations differed about two to three orders of magnitude.

Conclusions: Reduced fetuin-A levels are present in children with nephrotic syn-drome, associated with the degree of hypoalbumemia, and most likely due to reduced hepatic synthesis rather than urinary fetuin-A loss. Fetuin-A deficiency together with low 25-Hydroxyvitamin D3 levels may contribute to the cardiovascular morbidity in nephrotic children.

PS3-SAT-020

Bladder volume wall index in children with urinary tract infection

N. Hooman* ¹, S. H. Mostafavi², F. Hallaji², H. Otukesh¹

¹Department of Pediatric Nephrology, Ali-Asghar Children Hospital, Tehran University of Medical Science, Tehran, Iran, ²Department of Pediatric Radiology, Ali-Asghar Children Hospital, Tehran University of Medical Science, Tehran, Iran

Objective: To evaluate the bladder volume wall index in children with single and recurrent urinary tract infection.

Patients & methods: 100 children (8 boys, 92 girls) aged 4–15 years with history of urinary tract infection, 39 (20 male, 19 female) age matched healthy children with negative urine culture in previous month were enrolled in the study after taking consent from the parents. Kidney and bladder sonography were performed in all children. Bladder volume wall index was measured for which the result of 70–130 was presumed normal. Student T-test was used to compare means. Chi-square, likelihood ratio, and risk ratio were used for any rows x any columns tables. The measured data are presented as quartile. P-value <0.05 was considered significant.

Results: The mean bladder volume was 262.5(±82) in recurrent urinary tract infection, 235(±54) in single urinary tract infection, and 278(±80) in controls (P < 0.05). The mean wide of empty bladder was significantly higher in children with urinary tract infection (P < 0.05).The bladder was thick (<70) in 37 (28 cases, 9 controls) and it was thin (>130) in 38 (31 cases, 10 controls) (P > 0.05). The mean residue was not different between groups. The abnormal BVWI in children with vesicoureteral reflux was 74% compared to 49% in those without reflux (RR = 1.5; P < 0.05).

Conclusion: Children with urinary tract infection and abnormal bladder volume wall index high likely to have vesicoureteral reflux.

PS3-SAT-026

The definition of inflammanory process activity at children with chronic pyelonephritis

O. Bykova¹, A. Nee¹, V. Luchaninova* ¹, O. Semeshina²

¹Vladivostok State Medical University (VSMU), Vladivostok, Russion Federation, 2Uro-Nefrology Centre, Vladivostok, Russion Federation

Objectives and study: The tubular-interstitial component can be divided in 3 interconnected stages: inflammatory cells infiltration of nephritic interstition, interstitial fibrosis and forming of tubular atrophies as a result of immune and not immune factors interaction. Most significant factor is the tumor necrosis factor (TNF). The purpose—to study a level of TNF and TNF receptor-2 (sTNFR75) in urine at children with chronic pyelonephritis.

Methods: 65 patients with chronic pyelonephritis range in age from 19 months to 16 years old are surveyed. 37 patients (1 gr.) group—with relapse of disease, 12 (2 gr.)—with incomplete remission, 3rd—16 (3gr.)—with full chronic pyelonephritis remission. The control group is presented by 29 healthy children. Immunoenzimic analysis \“Multiscon\” (France) was used.

Results: The analysis of the received data has revealed authentic increase of TNF production at all patients in comparison with control group (9,1 ± 1,2; 8,0 ± 2,3; 6,9 ± 1,2; 4,9 ± 0,9 Ed accordingly) (p < 0,01). The urine level of sTNFR75 was authentic decreased on all patients (708,1 ± 37,2; 710,2 ± 22,3; 727,4 ± 28,6; 734,6 ± 29,9 Ed accordingly) (p < 0,01). It was the most decreased sTNFR75 level in 1 gr. Increased urine TNF level and decreased sTNFR75 are demonstrated of balance infringement between pro- and anti-inflammatory cytokines and persistance of inflammatory process in kidneys.

Conclusions: Inflammatory process and fibrogenesis were active in kidneys at chronic pyelonephritis children not only in an active stage of disease, but also in the stage of incomplete and full remission. Therefore definition of the given urine indicators in dynamics can be used as a marker of chronic pyelonephritis progress. It will help in estimation of treatment efficiency and timely correction.

PS3-SAT-027

Mid aortic syndrome—report of successful angioplasty

S. Minson* ¹, D. Roebuck², C. McLaren², K. Tullus¹

¹Department of Paediatric Nephrology, Great Ormond Street Hospital for Children, London, UK, ²Department of Interventional Radiology, Great Ormond Street Hospital for Children, London, UK

Objectives: We present a case (ST) of near complete atresia of the abdominal aorta presenting in infancy. He presented in severe heart failure and was initially felt to have a very poor prognosis. Despite that he has responded extremely well to a combination of interventional and medical therapy.

Results: ST presented at 4 months of age with cyanosis, sweating when feeding, and failure to thrive. He had marked hypertension and a significant pressure gradient between upper and lower limbs of 120/60 mmHg. CT scanning revealed near complete atresia of the abdominal aorta from T10 for 4 cm. The cardiac team advised this was too severe for surgical repair and palliative care was planned. He was referred to the renovascular team for further evaluation and his hypertension was partially controlled with 3 antihypertensive agents. At 5 ½ months he underwent angiography. Sucessful recanalisation and dilatation of the aorta was achieved to 5 mm with balloon angioplasty. Post angioplasty cardiac investigations showed normalization of cardiac function and DMSA scan showed normal isotope uptake bilaterally. He has required 3 further angioplasty procedures, and still needs 2 antihypertensive agents to control his blood pressure. His renal function remains normal and at age 6 years he has an excellent quality of life with normal growth and development.

Conclusions: MAS is a rare condition often presenting with severe hypertension, characterized by marked narrowing of the abdominal aorta. Previous studies have shown only limited success with PTA indicating failure to provide lasting clinical and angiographic improvement. In this child PTA has produced significant and sustained improvement in aortic calibre and blood pressure although he has needed repeat procedures and may require surgical intervention later. We describe a case illustrating that PTA and medical treatment can give an excellent treatment response with normal growth, development and quality of life.

PS3-SAT-030

Urinary tract infections in children and the risk of ESRF: a reappraisal of the evidence

J. Round* ¹, A. Fitzgerald², C. Hulme³, M. Lakhanpaul⁴, K. Tullus⁵

¹University College London, London, UK, ²New Zealand Guidelines Group, Wellington, New Zealand, ³Leeds University, Leeds, UK, ⁴Leicester University, Leicester, UK, ⁵Great Ormond Street Children’s Hospital, London, UK

Objectives: Paediatric guidance on diagnosis and treatment of urinary tract infections (UTIs) has in the past largely focused on identifying those children with vesicoureteral reflux, who are thought to be at greatest risk of renal scarring. However, this practice has been questioned; specifically the accepted association between UTI and end-stage renal failure (ESRF) through renal scarring. The aim of this study is to ascertain whether we can predict with confidence the true level of risk that a child with a first time UTI will develop ESRF as a result of that infection.

Methods: Using data available from renal registries an analytical approach based on previous estimates of risk is used to demonstrate the range of plausible estimates of risk that can be generated and levels of uncertainty that surrounds those estimates.

Results: Estimates of the perceived risk of developing ESRF following UTI range from 1/154 to 1/199900 and are heavily dependent on the assumptions made and the source of data.

Conclusion: There is considerable uncertainty in the relationship between childhood UTI and risk of ESRF based current data. The United States Renal Data System (USRDS) registry provides the greatest detail in defining the causes of ESRF and the estimate of risk based on this registry provides arguably the most reliable estimate, though it is an outlier compared with other estimates. If data were available from other registries with the same detail as the USRDS, it is probable that the estimates of risk would move towards the outlier. Registers that separate acquired from congenital renal scarring are needed, to establish the true risk of childhood UTI leading to ESRF and to guide clinical management. Until further evidence is available clinicians will continue to debate the risk of UTI and ESRF and consensus opinion will continue to guide management.

PS3-SAT-031

Living donation and low donor age lead to a decreased severity of arterial hypertension after pediatric kidney transplantation

N. Heidotting¹, T. Ahlenstiel¹, L. Pape* ¹

¹Department of Pediatric Nephrology, MEdical School of Hannover, Germany

Hypertension after pediatric renal transplantation (KTX) is common and constitutes one of the main risk factors for the development of interstitial fibrosis / tubular atrophy and cardiovascular disease. Several risk factors have been described for hypertension after transplantation, but, to date, no study has investigated the pre-transplant and transplant risk factors for arterial hypertension in children after KTX.

A retrospective chart review was performed of 485 children who underwent renal transplantation between 1974 and 2007. Patients smaller than 120 cm were excluded as no validated percentiles for blood pressure existed. Complete data sets were available for 144 patients. Data were recorded at 6, 12, 24 and 36 months after transplantation. We analysed the influence of donor age, age at transplantation, preemptive transplantation, living or deceased transplantation, and GFR on ambulant blood pressure monitoring (ABPM), the numbers of antihypertensives used, and the presence of end organ damage. Data was analysed by multivariance analysis and ANOVA. We found a statistically significant association between donor age and the need for antihypertensive medication (p = 0.001) and long-term end organ damage (p = 0.001). In multivariance-analysis, transplantation from living donors and preemptive transplantation were associated with the need for less antihypertensive medication (p = 0.001). Low recipient age was the only factor associated with lower 24 h ABPM (p = 0.001). Type of immunosuppressive regimen and GFR had no influence on the blood pressure.

The risk of arterial hypertension in children after KTX could be reduced by using organs from living and younger deceased donors.

PS3-SAT-032

Comparison of renal ultrasound with fluoroscopic voiding cystourethrography for the detection of vesicoureteral reflux in infants

J. Masalskiene* ¹, B. Pundziene¹, G. Verbliugeviciute¹

¹Clinic of children diseases, Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Kaunas, Lithuania

Background and objective: The aim of this study was to determine whether the morphologic changes on renal ultrasound (US) was a reliable sign for predicting primary vesicoureteral reflux (VUR) in infants after first acute pyelonephritis (APN).

Material and methods: We retrospectively collected and reviewed the demographic data, US and voiding cystourethrogram (VCUG) results of all infants, aged 1 month to 1 year old, who were admitted to Clinic of Children diseases with their first episode of APN, dated from January 2005 through December 2008. US was performed no later than 10 days after diagnosis of APN. The US results were considered positive even when the morphologic changes were minimal and were classified into five groups. Patients continued to receive antibiotic prophylaxis until fluoroscopic VCUG was performed. VUR at VCUG was graded using the International Reflux Study Committee System.

Results: There were 207 infants (91 (44%) male and 116 (56%) female) eligible for the study. A total of 112 ultrasound studies (54.1%) yielded negative results, 95 (45.9%) showed abnormalities and 25 infants had more than one changes in their kidneys. VCUG was done for 105 (50.7%) infants and the prevalence of VUR was 54.2%. We found statistical significant correlations between 4 group (dilatation of renal pelvis and/or calyxes) and grade IV reflux (r = 0.283, p = 0.001 < 0.05), and grade V reflux (r = 0.162, p = 0.020 < 0.05). The sensitivity of an ultrasound to detect VUR was 59.6%, but specifity was only 20.5%.

Conclusions: Dilatation of renal pelvis and/or calyxes was associated with severe VUR. We recommended an ultrasound for all infants with a first UTI. We concluded that infants with a history of renal pelvis dilatation and hydronephrosis should be investigated with VCUG.

PS3-SAT-035

Identification of two novel genetic factors for CAKUT origin: results from the AGORA project

K.Y. Renkema* ^1,2, E.M.H.F. Bongers¹, I.A.L.M. van Rooij³, A.M. van Eerde², W.F.J. Feitz⁴, A. Schedl⁵, H. McNeill⁶, F. Schaefer⁷, B. Franke¹, N.V.A.M. Knoers²

¹Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, ²Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands, ³Epidemiology, Biostatistics, and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, ⁴Pediatric Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, ⁵Inserm U636, Nice, France, ⁶Samuel Lunenfeld Research Institute, University of Toronto, Toronto, ON, Canada, ⁷Pediatric Nephrology, Heidelberg University Hospital, Heidelberg, Germany

Congenital Anomalies of the Kidneys and Urinary Tract (CAKUT) occur frequently in man and comprise the most common cause of end-stage renal disease in children. Structural disorders belonging to the spectrum of these anomalies include renal agenesis, multicystic dysplastic kidney, ureteropelvic junction obstruction, and duplex collecting system. Not much is known about the origin of CAKUT. In approximately 10% of CAKUT cases, renal abnormalities are found in close relatives, showing a strong genetic contribution to CAKUT origin. Alterations in genes expressed during nephrogenesis are considered to be important, with the final phenotypic outcome depending on additional modifying genetic and environmental factors. The aim of this study is to identify new genetic factors involved in CAKUT aetiology. From the AGORA biobank of the Radboud University Nijmegen Medical Centre over 700 well-documented CAKUT case-parent triads and 10 families with multiple affected members were recruited, comprising the largest CAKUT cohort world-wide. Mutation analysis of two novel CAKUT candidate genes was performed and revealed interesting genetic variants. Whole-exome sequencing in CAKUT families identified variants possibly involved in CAKUT aetiology. In addition, linkage analysis of a large CAKUT family demonstrated suggestive linkage for a locus on chromosome 4. The present identification and characterization of new genetic factors for CAKUT contributes to the understanding of the pathogenesis and the design of genetic diagnostic screening tests, facilitating early detection and recurrence risk estimations for CAKUT.

PS3-SAT-037

Microalbuminuria in children with primary and white-coat hypertension

T. Seeman* ¹, M. Pohl², U. John²

¹Department of Paediatrics, 2nd School of Medicine, Charles University Prague, Czech Republic, ²Department of Paediatrics, Friedrich-Schiller-University, Jena, Germany

Objectives of the study: Microalbuminuria should be investigated according the new guidelines of the European Society of Hypertension (ESH) in all hypertensive children. It serves as an early marker of hypertension-related renal damage in adults as well as children with primary hypertension. Data on the prevalence of microalbuminuria in hypertensive children are scarce and data on microalbuminuria in children with white-coat hypertension (WCH) are lacking. The aim of our study was to investigate the prevalence of microalbuminuria in children with primary hypertension (PH) and WCH.

Methods: Data on children with PH and WCH from two paediatric nephrology centers were retrospectively reviewed. Untreated children with PH and WCH confirmed by ambulatory 24-hr blood pressure monitoring (ABPM) who have had urinary albumin excretion (UAE) measured were included.

Results: Thirty-five children (28 boys) with hypertension were included (26 children PH, 9 WCH). Pathological microalbuminuria (>3.2 mg/mmol creatinine) was present in 20% of children with PH and none of the children with WCH (p < 0.05) The median UAE was higher in children with PH in comparison to children with WCH (1.27 ± 1.92 vs. 0.63 ± 0.43 mg/mmol creatinine, p < 0.05). No significant correlation was found between UAE and ambulatory BP SDS values or office blood pressure values. 19 children (54%) had hyperfiltration (estimated creatinine clearance >120 ml/min/1.73 m²). A positive correlation was found between ambulatory daytime and 24-hour diastolic BP and estimated creatinine clearance (r = 0.51 and r = 0.40, p < 0.05 for both).

Conclusions: Children with PH have often microalbuminuria. In contrast, children with WCH do not show elevated urinary albumin excretion. Microalbuminuria should be measured in all hypertensive children.

PS3-SAT-042

An 8-year-old boy with cataract, horseshoe kidney, obesity and hypertension; is it Bardet-Biedl syndrome?

A. Elmaghrabi* ¹, Y. Alassad², Z. El-Roubi¹

¹University of Medical Sciences and Technology, Khartoum, Sudan, ²University of Ribat National University, Khartoum, Sudan

We report a case of an 8-year-old boy with cataract, horseshoe kidney, obesity and hypertension. Patient was diagnosed with bilateral cataract at 7 years of age; he was noted to be hypertensive before surgery and accordingly was referred to the pediatric department for further evaluation and management of his hypertension in August of 2010. An extensive workup revealed normally functioning horseshoe kidney. His Serum Renin, Aldosterone and Aldosterone/renin ratio were within normal limits. Hormonal studies were normal except for slightly elevated evening cortisol. He was started on antihypertensive with good control, and cataract surgery for both eyes was done in March of 2010.

He was referred to our clinic in July of 2010 due high blood pressure (120/95) despite antihypertensive medication (Ca-channel blocker). On examination his body mass index (BMI) was above the 97% (obese range), he did have truncal obesity with a waist circumference of >70 cm. we obtained an echo which revealed normal heart with no left ventricular hypertrophy. Lipid profile revealed slightly elevated cholesterol. Computerized Tomography Angiogram (CTA) scan was obtained to exclude renovascular etiology for his hypertension, revealing a right accessory artery but no stenotic right or left renal arteries. Parents were advised on lifestyle modification in addition to his medication, his blood pressure normalized after a few months of lifestyle modification and stayed within normal range after weaning off the antihypertensive up to the report of this case. Though his BMI was still in the obese range, the cholesterol level in February of 2011 was within normal limits. In conclusion our patient has features of Bardet-Biedl syndrome, which include; obesity often with hypertension, ocular abnormalities (cataract) and renal anomalies (horseshoe kidney). Also we found CTA a useful noninvasive technique that can be used in children to visualize the renal vessels.

PS3-SAT-055

Prenatally detected hydronephrosis: what happens to the contralateral kidney

N. Girotto* ¹, S. Grbac-Ivanković¹, A. Smokvina¹

¹Clinical Department of Nuclear Medicine, Clinical Hospital Centre Rijeka, Rijeka, Croatia

Objectives: MAG3 diuretic scintigraphy is a well established diagnostic tool in pediatric nephrourology, frequently used in the evaluation of prenatally diagnosed hydronephrosis. The decision on operative treatment may depend on information obtained from the renogram. The Aim of this study was to evaluate renographic parameters obtained from contralateral, normal renal units (RUs), from newborn to the age of 3 years.

Patients and methods: Thirty three children including twenty newborns (mean age 28 days), referred to the first MAG3 diuretic scintigraphy due to unilateral kidney disease, entered the study. Only contralateral, sonographically normal RUs (N = 33) were analyzed on repeated scintigraphies. Altogether, a total of 78 dynamic studies were included. Kidney length and renographic curve parameters (T max and T1/2 max) were evaluated and statistically analyzed for different age groups: 7–28 days, up to two months, 2–12 months, second year, third year and 4–6 years.

Results: The results showed that kidney growth is most prominent during the first year of life, with an average length increase for 1.5 cm. In the following years, the growth is less prominent, up to 0.9 cm per year. In the newborn period there is a significantly shorter T max (mean T max 3.65 min) compared with the next age group (up to12 months; mean Tax = 4.8 min), and after that period gradually shortens reaching adult values by the age of 36 months. On the contrary, T1/2 max is significantly longer in newborn and early infant period than in older age groups.

Conclusions: It is important to be aware of the diversities of normal renographic curve pattern in early childhood, especially in the elimination part. Therefore, one should also consider other parameters like kidney growth, morphology and differential function to discern between normal and pathologic finding.

PS3-SAT-057

Low agreement between cardiologists diagnosing left ventricular hypertrophy in children with end stage renal disease

N. Schoenmaker* ¹, H. van der Lee², J. Groothoff¹, G. v Ieperen³, R. Tanke⁴, I. Frohn-Mulder⁵, J. Ottenkamp⁶, I. Kuipers⁶

¹Department of Pediatric Nephrology, Emma Children’s Hospital AMC, Amsterdam, The Netherlands, ²Department of Pediatric Clinical Epidemiology, Emma Children’s Hospital AMC, Amsterdam, The Netherlands, ³Deparment of Pediatric Cardiology, Wilhelmina Children’s Hospital UMCU, Utrecht, The Netherlands, ⁴Department of Pediatric Cardiology, UMC st. Radboud, Nijmegen, The Netherlands, ⁵Department of Pediatric Cardiology, Erasmus MC Sophia, Rotterdam, The Netherlands, ⁶Department of Pediatric Cardiology, Emma Children’s Hospital AMC, Amsterdam, The Netherlands

Objectives and study: Left ventricular hypertrophy (LVH) is an important diagnostic and prognostic finding in children with end stage renal disease (ESRD). In a multicenter project to improve the quality of care for children with ESRD, the prevalence of LVH appeared to differ considerably between centers. Therefore, we assessed the intra and inter observer reproducibility of the diagnosis LVH.

Methods: Digital images of the echocardiograms of 92 children with ESRD from 4 different centres were analyzed off-line by three observers. Because of low reproducibility two observers assessed one specific selected image and all images from twenty echocardiographies. Kappa was calculated. The measurement errors are expressed as Smallest Detectable Change (SDC).

Results: Kappa ranged from 0.1–0.4, which is considered low. The intra observer SDC ranged from 1.6–1.7 and from 1.3–2.6 mm for IVSd and LVPWd, respectively. The inter observer SDC were 2.4 and 2.6 mm. For selected images the intra observer SDC ranged from 1.0–1.3 and from 0.7 to 2.1 mm, the inter observer SDC were 2.1 and 2.3 mm.

Conclusions: Agreement between observers diagnosing LVH using conventional echocardiography is low. In individual children changes in diastolic wall thickness smaller than 1.6 mm cannot be distinguished from measurement error, even when measured by the same observer. This limits the use of echocardiography to detect changes in IVSd or LVPWd in children with ESRD.

PS3-SAT-058

Diastolic function measured by tissue doppler imaging in paediatric patients with end stage renal disease

N. Schoenmaker* ¹, I. Kuipers², M. Tromp¹, H. van de Lee³, J. Ottenkamp², J. Groothof¹, RICH-Q studygroup

¹Department of Pediatric Nephrology, Emma Children’s Hospital AMC Amsterdam, The Netherlands, ²Department of Pediatric Cardiology, Emma Children’s Hospital AMC Amsterdam, The Netherlands, ³Department of Pediatric Clinical Epidemiology, Emma Children’s Hospital AMC Amsterdam, The Netherlands

Objectives and study: Cardiovascular disease is the main cause of death in patients with End-Stage Renal Disease (ESRD). The aim was to compare the prevalence of left ventricular hypertrophy (LVH)and diastolic dysfunction(DD)in children with ESRD and healthy children using conventional echocardiography and Tissue Doppler Imaging (TDI).

Methods: 32 children with ESRD and 79 healthy control subjects, matched for weight or body surface area (BSA), were assessed with conventional echocardiography and TDI. Parameters related to LVH (IVSd%, LVPWd% and LV mass index) and DD (E/a ratio and E/e′ ratio) were compared in the ESRD and control groups using linear regression analysis.

Results: The children with ESRD were significantly older than their healthy controls with the same weight or BSA, mean difference (MD) 2.6 years (p = 0.015). After adjustment for age, the ESRD patients had a smaller MV E/a ratio (MD 0.32, p = 0.007) and larger IVSd% (MD 20.9, p < 0.001), LVPWd% (MD 19.7, p < 0.001), LV mass index (MD 18.1, p < 0.001) and E/e′ ratio (MD 2.5, p < 0.001) than the control subjects. LVH was diagnosed in 3 of the 31 children (10%) with ESRD and none of the controls (p = 0.04). DD was diagnosed in none of the children according to the E/a ratio. According to the E/e′ratio 11/26 (42%) of the patients with ESRD and none of the controls were diagnosed with DD (p < 0.001).

Conclusion: Children with ESRD have significantly more LVH, larger IVSd%, LVPWd% and LV mass index, E/e′ ratio than healthy, BSA matched, controls. Tissue Doppler is more sensitive in the early detection of DD than conventional E/a ratio in patients with ESRD.

PS3-SAT-059

Audit of urine testing appropriateness in treatment of well infants with hyperbilirubinaemia

T. Chowdhury* ¹, H. Kisat², K. Tullus³

¹Kings College London, London, UK

Aim: This audit was carried out in order to investigate the appropriateness of urine testing in well infants with prolonged jaundice.

Methodology: This study was conducted retrospectively by analysing case notes and the microbiology database of urine culture results for well infants with prolonged jaundice at Pembury Hospital between 2004 & 2009. Possible UTI was described as the presence of white cells and/or growth > 10X105/l of single organisms. Data included the infants’ age, gender, the number of samples taken, the organisms cultured, microscopic findings and any further treatment or investigations. The Newcastle Urine Collector pack (urine collection pad) was used to obtain the samples.

Results: In total, 319 infants had prolonged jaundice. Of these, 22/319 (6.9%) had growth of any bacteria of which 12 were boys and 10 were girls. Of these cultures 8 showed growth of single organism >105 and 14 showed mixed organism growth. Three of the infants did have the presence of white cells in their urine. However, on repeating culture only one infant continued to show repeated single organism growth with white cells present each time. This infant was treated with antibiotics and had further investigations, including an ultrasound scan and radionuclide cystogram, showing a small right kidney with a pronounced right renal pelvis and small bladder. However, there was no further documentation in the notes showing any clinical manifestations of infection or full dosage treatment for a UTI.

Conclusions: Urine culture was rarely positive in well infants with prolonged jaundice. Since only 1/319 of the infants had a significant UTI it may be inappropriate to request urine testing in all infants with prolonged jaundice although recent NICE guidelines recommend this practice. Devising a protocol to select unwell babies for urine microscopy may be more efficient and cost-effective rather than routine culture on all infants.

PS3-SAT-107

N-terminal fragment of pro-brain natriuretic peptide (NT-ProBNP) is better marker of ventricular dysfunction than left ventricular mass (LVM) in children undergoing dialysis

A. Alonso* ¹, C. Peralta¹, J. Rivas², C.G. Meseguer¹, C. Fernández¹, L. Espinosa¹, M. Navarro¹

¹Pediatric Nephrology Department, Hospital La Paz, La Pz, Spain, ²Pediatric Cardiolgy Department, Hospital La Paz, La Paz. Spain

Objectives and study: NT-ProBNP is an independent marker of fluid overload, myocardial damage, morbidly and mortality in adult population on dialysis; however, blood accumulation in renal insufficiency makes difficult its interpretation. Isolated studies in children have shown a relationship with increase of LVM. The aim of this study is to evaluate the predicting value of ventricular systolic or diastolic dysfunction in children on dialysis.

Patients: 15 children on hemodialysis (6)or peritoneal dialysis(9) aged 9.48 ± 5 years were studied. The follow up on dialysis was 27 ± 31 months. Hypertension was found in 66%, left ventricular hypertrophy (LVH) in 46% and ventricular dysfunction in 33%. 60% of the patients had some type of cardiovascular event: acute lung oedema, cardiac insufficiency or hypertensive emergency.

Results: We found higher LVM in hypertensive patients 107 ± 66 versus 48 ± 13 gr/m2; Z score: 2.2 versus −1.44). Hypertensive patients had higher levels of NT-proBNP: 14407 ± 14000 versus 4423 ± 5084 pg/ml and troponin i: 0.11 ± 0.2 versus 0.03 ± 0.1 ng/ml. Relative risk [RR] of ventricular dysfunction were increased in patients with NT-ProBNP levels higher than 5500 pg/ml [RR = 2.5]. Previous cardiovascular events [RR = 2.5] and LVH [RR = 2] were also associated with ventricular dysfunction. We did not find any relationship between NT-proBNP levels and gain of weight among dialysis sessions, hypotension episodes, residual renal function, primary disease, modality and dose of dialysis, haemoglobin or PTH.

Conclusions: NT-ProBNP values higher than 5500 pg/ml are markers of myocardial dysfunction in children on dialysis.

PS3-SAT-068

Renal function in children with a solitary functioning kidney assessed by inulin clearance—the KIMONO study

R. Westland* ¹, Y. Abraham¹, A. Bökenkamp¹, M. F. Schreuder², J. A.E. van Wijk¹

¹Department of Paediatric Nephrology, VU University Medical Center, Amsterdam, The Netherlands, ²Department of Paediatric Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Objectives and study: Children with a solitary functioning kidney (SFK) have an increased risk of developing chronic kidney disease (CKD). In daily clinical practice, glomerular filtration rate (GFR) is generally monitored using the Schwartz estimation equation (eGFR). In order to determine GFR in children with an SFK, a gold standard inulin clearance (Cinulin) was performed in the KIMONO study population and compared with eGFR.

Methods: 60 children underwent a single shot Cinulin with sampling at five set times after injection. Plasma clearance was obtained using Bayesian analysis. A matching eGFR on the day of Cinulin was calculated and corrected for gender and age. Differences between Cinulin and eGFR were analyzed by paired-samples t-test. Patients were classified by K-DOQI guidelines for CKD. Subsequently, this classification was compared between Cinulin and eGFR.

Results: At a mean age of 13.7 (standard deviation [SD] 4.4) years, mean Cinulin was 81 (SD 23) ml/min/1.73 m² and mean eGFR was 87 (SD 24) ml/min/1.73 m² (mean difference 6 [SD 21] ml/min/1.73 m²; p = 0.027). Based on Cinulin, 11 (18%) children had CKD stage 3 or worse (i.e. GFR <60 ml/min/1.73 m²) compared to 8 children (13%) based on eGFR (p = not significant). Misclassification in the stage of CKD between Cinulin and eGFR was identified in 28 (46%) patients (p < 0.001).

Conclusions: Our KIMONO study demonstrates that a large sample of children with an SFK have CKD stage 2 at a young age, with a considerable subgroup having at least CKD stage 3 based on Cinulin. eGFR overestimates GFR in these patients leading to misclassification in CKD stage. This illustrates the need for a paediatric eGFR equation for CKD 1 and 2 patients to monitor children with an SFK.

PS3-SAT-070

Gene analysis in children with a congenital solitary functioning kidney—the KIMONO gene study

R. Westland* ¹, P.J.G. Zwijnenburg², A.M.A. Lachmeijer², M.F. Schreuder³, J.A.E. van Wijk¹

¹Department of Paediatric Nephrology, VU University Medical Center, Amsterdam, The Netherlands, ²Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands, ³Department of Paediatric Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Objectives and study: Children with a congenital solitary functioning kidney (cSFK) represent a large sample of patients with congenital anomalies of the kidney and urinary tract (CAKUT). Recently, new genes have been identified in CAKUT. In order to clarify the importance of these genes in cSFK, we performed genetical analyses in children with a cSFK.

Methods: 46 unrelated children (unilateral renal agenesis: n = 21[46%] and multicystic kidney disease: n = 25 [54%]) were consulted by a clinical geneticist. Genetic analysis was performed based on the phenotype. HNF1β (n = 19), UMOD (n = 14), EYA1 (n = 2), SIX1 (n = 2), PAX2 (n = 1), NPH1 (n = 1), MLL2 (n = 1), TFAP2A (n = 1), CLCN16 (n = 1), CLCNKB (n = 1), FGFR3 (n = 1), URSM (n = 1), CHD7 (n = 1), GPC3 (n = 1) and/or FMR1 (n = 1) were analyzed. Chromosomal abnormalities were investigated in a number of patients by karyotyping (n = 16), MLPA-analysis for common microdeletions, including 22q11, (n = 15), array-CGH (n = 9) and FISH (n = 9) for 22q11-region. Furthermore, family histories were taken in all children. Renal ultrasound was performed in the parents and siblings of 22 (48%) children.

Results: Genetic abnormalities were identified in 9 (20%) children (22q11deletion-syndrome n = 2; Bartter-syndrome: n = 1; Branchiooculofacial-syndrome: n = 1; Cateye-syndome: n = 1; Fragile X-syndrome: n = 1; Glomerulocystic kidney disease: n = 1; Kabuki-syndrome: n = 1 and Urorectalseptum malformation: n = 1). In 23 (50%) children, a genetic syndrome was suspected without molecular confirmation. 13 (28%) children had a positive family history for CAKUT and 12 (55%) parents/siblings demonstrated CAKUT on renal ultrasound.

Conclusions: In this selected sample of children with a cSFK, genetic abnormalities/syndromes were identified in 20% of cases. This underlines the need for studies on whole genome analysis in CAKUT and cSFK in particular.

PS3-SAT-074

Impact of obesity on the severity of ambulatory hypertension in children and adolescents

K. Babinska* ¹. L. Kovacs¹, V. Janko¹, T. Dallos¹, J. Feber²

¹2nd Department of Pediatrics, Comenius University Medical School, University Children’s Hospital, Bratislava, Slovakia, ²Division of Nephrology, Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Canada

Objective: The goal of our study was to analyze the impact of obesity on the severity of hypertension in obese children and adolescents.

Methods: One hundred-nine patients with primary obesity aged 7 to18 years (mean ± SD age = 14.1 ± 3.1) were enrolled in the study. Patients were divided into 3 groups according to BMI Z scores: Group 1 (n = 27): BMI >1.65 and <3.28 SDS; Group 2 (n = 55): BMI >3.29 and <4.91 SDS; Group 3 (n = 27): BMI >4.92 SDS. Anthropometric and ambulatory blood pressure monitoring data (ABPM) were analyzed. Definition and staging of ambulatory hypertension was based on ABPM blood pressure levels and blood pressure load (BPL).

Results: Only 26 patients (24%) had ambulatory normotension, 27 (25%) had ambulatory prehypertension, 3 (3%) had hypertension and 53 (48%) had severe ambulatory hypertension. The severity of hypertension increased significantly with the degree of obesity (Chi square test for trend, p = 0.0027). Daytime systolic, diastolic and mean arterial pressures (SBP, DBP, MAP) increased significantly with increased BMI (shift to the right), whereas the nighttime pressure remained elevated regardless of the degree of obesity. Isolated nighttime hypertension was observed in 25% of patients, 38% were classified as non-dippers.

Conclusions: Almost 50% of children with obesity and hypertension detected on ABPM suffer from severe ambulatory hypertension. BMI has a major impact on the severity of hypertension and increase of daytime blood pressure.

PS3-SAT-080

Validity and reliability of pediatric lower urinary tract scoring system for Iranian children

N. Hooman* ¹, S. H. Mostafavi², F. Hallaji², H. Otukesh¹

¹Department of Pediatric Nephrology, Ali-asghar children hospital, Tehran University of Medical Sciences, Tehran, Iran, ²Department of Pediatric Radiology, Ali-asghar children hospital, Tehran University of Medical Sciences, Tehran, Iran

Purpose: Pediatric lower urinary tract scoring system (PLUTSS) is a questionnaire contains items for assessment of wetting episodes, voiding frequency and pattern. It is used for screening and evaluation of the response of children with lower urinary tract symptoms to therapy. We studied the validity and reliability of this questionnaire among Iranian children.

Materials and methods: One hundred and ninety-seven children (56 boys, 141 girls) aged 5–15 years with urinary tract infection, voiding dysfunction, enuresis were enrolled in study. Thirty-three healthy age-matched children (21 boys, 12 girls) without urinary complaint were considered as controls. PLUTSS was filled out for all children. Sonography was performed to rule out any urogenital abnormality. Internal consistency, test-retest reliability, and validity of the questionnaire were assessed using Cronbach’s alpha, intraclass correlation coefficiency, and ANOVA test respectively. Roc curve was used to define cut-point and its validity in discrimination between groups. P-value <0.05 was considered significant.

Results: The means PLUTSS were 6.8(±5.4 SD) in voiding dysfunction, 14.4(±5 SD) in enuresis, 10.5(±7.8 SD) in recurrent and 8.9(±6 SD) in single urinary tract infection, and 1.9(±1.8) in controls (P < 0.001). Cronbach’s alpha for the 14 items of questionnaire was 0.74. The intraclass coefficient correlation for assessing test-retest reliability was 0.82 (P < 0.001). ROC curve showed cut point of 5 for differing case from controls with sensitivity of 97.0 and specificity of 74.9(P < 0.001).

Conclusions: Persian translated PLUTSS has validity and reliability as an instrument for screening children with urinary tract symptoms but some questions need to change in some way to be understandable by our culture.

PS3-SAT-082

Extrarenal manifestations of autosomal dominant polycystic kidney disease (ADPKD)

S. Harutyunyan¹, E. Andreeva¹, N. Savenkova*¹, V. Larionova², G. Leviashvili¹

¹Saint-Petersburg State Pediatric Medical Academy, Department of pediatric nephrology, Saint-Petersburg, Russian Federation, ²Saint-Petersburg State Pediatric Medical Academy, Molecular diagnostics laboratory, Saint-Petersburg, Russian Federation

Aim of study: To identify the frequency and nature of extrarenal manifestations in children and adolescents (probands) and adults (first degree relatives) with ADPKD.

Methods: We estimated data of clinical, laboratory, ultrasound, computer tomography and magnetic resonance imaging examinations. 75 members of 37 families with ADPKD: 37 children (18 girls, 19 boys) aged between 1–18 years, and 38 adults (21 females, 17 males) aged between 25–50 years were included in our research.

Results: The mean age of renal cysts detection in probands was 9.0 ± 5,47 years. 7 ADPKD children (18.9%) were diagnosed either in utero (5.4%) or within the first 18 month of life (so called VEO—very early onset). The reasons of first abdominal ultrasonography were: family history of ADPKD in 17 children (included 2 cases of diagnostics in utero), presence of complaints (abdominal and/or loin pain) in 6, examination due to other diseases in 14 (eight with urinary system diseases). 20 (54%) probands inherited the ADPKD from mother, 16 (43.2%) from father, in one family both of parents were affected. Cysts in other organs were detected in 5 (13.2%) probands: 3 (7.9%) in liver, 2 (5.3%) in ovaries. 4 (10.8%) children had cardiovascular abnormalities (mitral valve prolaps, aortic root dilatation, redundant mitral chordae tendineae). Ocular pathology (abnormalities of refraction) presented in 11 (29.7%) from 37 probands. In 38 ADPKD adults cysts in other organs were detected in 50% of cases: 34.2% in liver, 7.9% in ovaries, 5.3% in brain, 2.6% in spleen.

Conclusions: Analysis of extrarenal manifestations in ADPKD revealed that occurrence of cysts in other organs in adults (50%) is fourfold more than in children and adolescents (13.2%).

PS3-SAT-086

Should the mean arterial pressure be included in the definition of ambulatory hypertension in children?

T. Sulakova* ¹, J. Feber²

¹Department of Pediatrics, Univ.Hosp.Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, The Czech Republic, ²Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Canada

Objective: The diagnosis of hypertension (HTN)/normotension (NT) on ambulatory blood pressure monitoring (ABPM) is usually based on evaluation of systolic (SBP) or diastolic blood pressure (DBP). The mean arterial pressure (MAP) is not frequently used in clinical practice despite the fact that it is directly measured by the oscillometric device and can be compared with normative values (Wuehl et al, 2002). The goal of the study was to analyze whether inclusion of MAP improves the detection of HTN on ABPM.

Methods: We retrospectively analyzed ABPM records in 229 children (116 boys), median age of 15.31 years, referred for evaluation of HTN. The diagnosis of HTN was made using two definitions: (A) if either MAP or SBP or DBP Z scores were ≥1.65 SDS (95th percentile) during 24 h or daytime or nighttime periods, (B) if either SBP or DBP Z scores were ≥1.65 SDS (95th percentile) during 24 h or daytime or nighttime periods.

Results: Using the definition A (including MAP), 46 patients had HTN and 183 patients had NT compared to the definition B (without MAP) by which only 37 patients had HTN and 192 patients had NT (Fisher exact test, p = 0.001). The level of agreement between the two definitions was very good; kappa = 0.86 ± 0.04; 95% CI 0.78–0.95. However, 9 out of 46 patients with HTN (19.5%) were missed by not using the MAP in the definition of HTN. These nine patients had only mild HTN with a median Z score of 1.69 SDS (range from 1.66 to 2.16).

Conclusions: The inclusion of MAP in the definition of ambulatory hypertension significantly increased the number of hypertensive patients. MAP may be very helpful in detecting mild HTN in patients with normal/borderline SBP and DBP.

PS3-SAT-091

Urinary nerve growth factor (NGF) level in children with neurogenic bladder

A. Korzeniecka-Kozerska*¹, T. Porowski¹, E. Tenderenda¹, W.M. Zoch Zwierz¹

¹Department of Paediatrics and Nephrology Medical University of Bialystok, Bialystok, Poland

Objectives: Clinical and experimental data have shown that the urinary bladder can stimulate production of NGF in various circumstances This study was performed to investigate the urinary level of NGF in patient with a neurogenic bladder (NB) after meningomyelocoele and to compare the results with a urodynamic data. We also wanted to determine whether urinary NGF can be a biomarker bladder overactivity.

Material and methods: Evaluation included urine analysis and urodynamic study in 28 children (median age 8.0 (range 2–17.5 years) with NB and 20 healthy patients (median age 11 (range 3–17 years). Urinary level of nerve growth factor were measured by ELISA and the results was normalized on creatinine concentration. The NGF/Cr level was compared among the different group. This study has been accepted by Ethical Committee Medical University of Bialystok.

Results: The estimated urinary NGF/Cr levels were very low in the control group (median 5.69 ng/mg range 1.13–58.82) and significantly higher in NB patients (median 62,19 ng/mg, range 3.2–253.56; p = 0.000) The level of NGF depended on the grade of overactivity confirmed by urodynamic investigation. This study has been shown positive correlation between NGF level and pressure of detrussor at cystometric capacity (r = 0,376086 p = 0,04856). There was no correlations between the doses of administered treatment and level of NGF. There was no differences in measured parameters between boys and girls too. The intravesical pressure during infusion didn’t exceed 20 mmH20. Despite of this the NGF level was significantly elevated compared to the control group.

Conclusions: In our study patients wit NB has significantly higher urinary NGF/Cr level compared to control. The level of NGF correlates with the intravesical pressure although it is in normal range and doesn’t show correlations with administered treatment. The measurements of urinary NGF level can well reflect the pressures in neurogenic vesical bladders.

PS3-SAT-093

Interleukin-6 (IL-6) and interleukin-8 (IL-8) in urine of children with acute pyelonephritis

A. Paripovic* ¹, N. Stajic¹, J. Putnik¹, B. Slavkovic¹, E. Jaksic¹, R. Bogdanovic¹

¹Institute of Mother and Child Healthcare of Serbia “Dr Vukan Cupic”, Belgrade, Serbia

Objectives: Aim to determine the urine concentrations of IL-6 and IL-8 in children with acute pyelonephritis (APN) and to investigate association of IL-6 and IL-8 concentrations with findings on static renal scintigraphy during acute pyelonephritis and after 6 months.

Methods: Methods prospective study was performed in period 1.8.2008.–1.3.2009 in 30 children with the 1st APN. Control group included 20 febrile children with normal urinalysis. IL-6 and IL-8 were measured with flowcytometric method and were expressed in relation to creatinuria on admission and 48 hours after start of treatment. Other analyses and exams included SE, CRP, FBC, urine sediment and culture, renal ultrasonography, voiding urethrocystography (VCUG), renal DMSA in acute phase and 6 months later. Nonparametric tests have been used for statistical analysis.

Results: Results mean age of patients (15 boys, 15 girls) was 10 ± 9 months On admisision, IL-6 concentration (median 439 pg/ml) and IL-8 (5634) were higher in patients with APN than in control group (0 and 563, respectively, p < 0,01) and higher after 48 hours of treatment then on admission (0 and 1077, p < 0,01). There was a statistic sigificant correlation between IL-6 on admission and changes on renal DMSA scan in acute phase but not with those on follow-up DMSA scan (p < 0,01). There wasn’t a correlation between IL-6 or IL-8 with presence vesicoureteral reflux on VCUG.

Conclusion: IL-6 and IL-8 may be useful in early diagnosis of APN in febrile children. Elevated concentration of IL-6 may indicate renal parenchyme involvement in acute phase, but not a permanent damage.

PS3-SAT-096

Hypertension in the Czech registry of renal biopsies (CCRB), 15 years of experience

A. Kolský* ¹, E. Jančová², J.Dušek³, M. Hladík⁴, S. Skálová⁵, K. Vondrák³, P. Geier⁶, V. Smrčka⁷, J. Štarha⁸, J. Skibová⁹

¹Dept. of Paediatrics, 3rd Medical Faculty, Charles University, FNKV, Prague, Czech Republic, ²Dept. of Nephrology, 1st Medical Faculty, Charles University, Prague, Czech Republic, ³Dept. of Paediatrics, 2nd Medical Faculty Charles University, Prague, Czech Republic, ⁴Dept. of Paediatrics, Teaching Hospital, Ostrava, Czech Republic, ⁵Dept. of Paediatrics, Medical Faculty, Charles University, Hradec Králové, Czech Republic, ⁶Dept. of Paediatrics, Medical Faculty, Palacky University, Olomouc, Czech Republic, ⁷Dept. of Paediatrics, Regional Hospital, České Budějovice, Czech Republic, ⁸Dept. of Paediatrics, Medical Faculty, Masaryk University, Brno, Czech Republic, ⁹Dept. of Statistics, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

Objectives and study: To analyze the occurence of arterial hypertension (HT) at the time of renal biopsy (RB). Methods: This report describes data collected by the National CRRB which includes 1903 RB in children and adolescents ≤18 years in the years 1994–2008. CRRB has been run since 1994 and includes currently all RB of native kidney in children in Czech Republic. Results: Mean age was 12.5 ± 4.5 yrs (2.5 months–18 yrs), boys were 55.5%. At the time of RB, 280 (14.7%) of the children were hypertensive (based on the Second Task Force, Pediatrics 1996). The mean age of patients with HT and sex distribution of patient with HT did not differ significantly from that of normotensive (NT) patients (12.6 ± 5.1 yrs vs. 12.5 ± 4.4 yrs), (HT boys 54.8% vs. 59.6% NT boys). Those with HT had higher serum creatinine levels (S-Cr, 140.3 ± 162.4 vs. 75.6 ± 61.8/μmol/l/, p < 0,001) and had significantly higher proteinuria (4.2 ± 5.2 vs. 1.9 ± 3.1 /g/24 h/, p < 0.001). The highest incidence of HT was found to be associated with postinfectious GN (30.8%), FSGS (28.7%), Henoch-Schönlein purpura (25.8%), Focal-segmental GN (24.6%), IgM nephropathy (23.5%), membranous GN (22.2%), SLE nephritis (22.0%) and membranous proliferative GN (20%). Clinically serious complications were in 2.8% of patients, no differences between HT and normotensives. Conclusion: Arterial hypertension is associated with known risk factor of progression of biopsy-proven GN such as S-Cr or proteinuria. RB provides us important information about the epidemiology of glomerulonephritis in our region, about indications for performing RB and represents a base for co-operation in this field.

PS3-SAT-098

In vivo susceptibility of ESBL producing E. coli to ceftriaxone in children with acute pyelonephritis

A. Peco-Antić* ¹, D. Paripović², S. Buljugić³, B. Spasojević², M. Cvetković², S. Laban-Nestorović⁴, G. Miloševski-Lomić²

¹University Children’s Hospital, Medical Faculty, University of Belgrade, Serbia, ²University Children’s Hospital, Nephrology Department, Belgrade, Serbia, ³University Children’s Hospital, Belgrade, Serbia, ⁴University Children’s Hospital, Microbiology Department, Belgrade, Serbia

Introduction: The choice of empiric therapy of acute pyelonephritis (APN) in children should be based on the knowledge of Escherichia coli (E. coli) as the most common uropathogen and its antibiotic sensitivities, considering that nowadays ESBL-producing [ESBL (+)] E. coli is on the rise worldwide.

Objectives: To examine in vivo susceptibility of ESBL (+) E. coli to ceftriaxone (CTX), and to evaluate the options for empiric therapy for APN in children.

Methods Retrospective study of CTX empiric therapy on APN in children treated at University Children΄s Hospital in Belgrade from January 2005 to December 2009. ESBL phenotypic confirmatory test with ceftazidime, CTX and cefotaxime was performed for all urine isolates by disc diffusion method on Mueller-Hinton agar plates. A ≥5 mm increase in a zone diameter for antimicrobial agent tested in combination with clavulanic acid versus its zone when tested alone was considered indicative of ESBL production. In vivo sensitivity of CTX documented by clinical response to empiric CTX therapy was compared between two groups of children: group I with ESBL (+) and group II with ESBL (−) APN.

Results: Group I with ESBL (+) APN consisted of 94 patients and group II of 120 patients with ESBL (−) APN, respectively. All patients received CTX as empiric therapy at a mean dose of 66.9 mg during 7.2 ± 2.6 days of therapy. Clinical effect of CTX was similar in patients with ESBL (+) compared to those with ESBL (−) APN.

Conclusion: Microbiological in vitro resistance of ESBL E. coli to CTX determined by standard methods is not sufficiently predictive for its in vivo sensitivity. Therefore CTX may be used as empiric therapy for acute pyelonephritis in children.

PS3-SAT-108

Prognostic markers in unilateral ureteropelvic junction obstruction

Y. Bayram¹, A. Karabay Bayazit* ¹, A. Noyan¹, S. Yavuz¹, R. Anarat², A. Anarat¹

¹Cukurova University, School of Medicine, Department of Pediatric Nephrology, Adana,Turkey, ²Başkent University, Central Laboratory, Adana Hospital, Adana, Turkey

Objective: In the present study, it is aimed to determine the correlation between urine excretion of MCP-1, TGF-ß1 and the severity of the ureteropelvic junction obstruction in operated and non-operated children diagnosed as unilateral ureteropelvic junction obstruction.

Material and methods: Twenty operated and 26 non-operated patients with unilateral ureteropelvic junction obstruction and 22 healthy children within similar ages were included in the study. MCP-1, TGF-β1 and creatinine were concurrently measured in the urine samples of both patient and healthy controls.

Results: The ratio of urine MCP-1/creatinine and TGF-β1/creatinine was statistically higher in operated patients compared to non-operated patients and healthy children (p < 0,05). No statistical difference was found between the non-operated and control groups (p > 0.05). There was no significant correlation between the ratio of urine MCP-1/ creatinine and antero-posterior diameter of pelvis (p > 0.05). Urine levels of TGF-β1 was weakly correlated with antero-posterior diameter of pelvis (p < 0,05).

Conclusion: Urine MCP-1 and TGF-β1 might be used as prognostic markers in the follow-up of children with unilateral ureteropelvic junction obstruction particularily for determination of the time of the surgery.

PS3-SAT-111

Duplex collecting system in a series of children

B. Kasap* ¹, A. Bal², C. Alparslan², M. Anıl², A.B. Anıl², Ö. Yavaşcan¹, N. Aksu¹

¹Tepecik Research and Training Hospital Division of Pediatric Nephrology, Izmir, Turkey, ²Tepecik Research and Training Hospital Department of Pediatrics, Izmir, Turkey

Introduction: Duplex collecting system (DCS) is one of the most frequent abnormalities associated with urinary system in children. This anomaly is infrequently accompanied by ureterocele, vesicoureteral reflux (VUR), ectopic ureter, kidney stone disease (KSD), urinary tract infections and some genetic syndromes. We reported a series of children with DCS.

Patients and methods: The data of patients with DCS between 1996 and 2010 were reviewed retrospecitvely indicating the side (unilateral/bilateral), the nature (complete/partial) of DCS, presenting symptoms, imaging techniques and the number of experienced operations.

Results: DCS was reported in 51 patients (M/F: 15/36). Twenty-two (43%) of them had right-sided, 21 (41%) had left-sided and 8 (16%) had bilateral DCS. In 21 patients of whom the introduction of the ureters into the bladder could be demonstrated, 12 had imcomplete, 9 had complete DCS. Presenting symptoms were UTI in 30, nocturnal enuresis in 2, diurnal enursis in 2, KSD in 3 and due to other miscallenous reasons in 14 of the patients. The imaging modalities used in patients were MRU in 2, VCUG in 3 and IVP in other patients. Accompanying VUR was found in 10, ureterocele was found in 3 of the patients. Interestingly, none of the patients had ureterocele along with VUR or ectopic ureter. In 6 (14%) of the patients with unilateral DCS hipogenesis/agenesis was found. Surgical interventions included partial nephrectomy in 2, ureteroureterostomy in 1 and anti-reflux surgery in 3 o f the patients. One patient had atrial septal defect and another had Noonan Syndrome.

Conclusion: DCS may present with many different clinical symptoms and Weigert-Meyer rule is not constant in all patients with DCS. The diagnosis may be established via different radiological moieties other than IVP.

PS3-SAT-112

Temocillin as first-line treatment in children with first episode of urinary tract infection (UTI)

B. Chiodini* ¹, P. Lepage¹, G. Mascart¹, M. Hall¹, K. Ismaili¹

¹Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Bruxelles, Belgium

Objectives and study: There is lack of information concerning the efficacy of Temocillin as first-line treatment of UTI. Temocillin covers most Gram-negatives, but is inactive against Gram-positives and anaerobic germs. The objective of the study is to assess the efficacy of Temocillin as first-line antibiotic in the treatment of first febrile UTI episodes in children.

Methods: This prospective 2-years study was designed as a quality control of our current central practice on UTI treatment. We characterised in children ≥1 year and treated with Temocillin, the frequencies of uropathogens and their antimicrobial resistance rates, in particular for Temocillin. These same characteristics have also been analysed for children <1 year and not treated with Temocillin.

Results: 75 children ≥1 year with first febrile UTI were treated with Temocillin. The most common pathogen was Escherichia Coli, which grew in 70 (93%) cultures. Resistance rate to Ampicillin was as 53%. Of all pathogens, only 1 was Gram-positive, potentially Temocillin-resistant. MIC was ≤16 μg/ml for all the pathogens, and was ≤4 μg/ml in 92% of cases. Characterisation of the pathogens and antibiotic susceptibility testing was also performed in 115 children, <1 year and not treated by Temocillin. Again, of all pathogens, only 1 was Gram-positive, potentially Temocillin-resistant. MIC was ≤16 μg/ml for all the pathogens, and was ≤4 μg/ml in 90% of cases.

Conclusion: In spite of its narrow spectrum, Temocillin appears as an excellent first-line therapy of UTI in children as it efficiently covers almost all bacteria isolated from the urinary tract in our series, even including children under 1 year of age.

PS3-SAT-113

Can early cardiovascular changes be prognostic criteria in pediatric patients with systemic lupus eritematosus?

B. Sozeri* ¹, M. Deveci², S. Mir¹

¹Ege University Faculty of Medicine Department of Pediatric Nephrology, Izmir, Turkey, ²Ege University Faculty of Medicine Department of Pediatric Cardiology, Izmir, Turkey

Systemic lupus eritematosus(SLE)has a bimodal pattern of mortality. Llater-onset deaths aredue to morbid cardiovasculardisease(CVD)such as left ventricular hypertrophy(LVH.Autoantibodies andcirculating immune complexes,have all been identified as important factors.Our aim was to determine presence of cardiovascular changes in children with SLE. We investigated functional and morphological changes in cardiovascular system.

Twentypatients (4 male,16 female) withSLE and 25 controls were included to the study. Arterial stiffness(As) was evaluated by carotid-femoral pulse wave velocity(PWV) andaugmentation index(AIx.)The mean age was 13.7 ± 3.46 years. The mean duration of disease was 10.7 ± 2.46 years. Three patients had hypertension.The mean PWV and AIx were higher in patients than in controls[(6.56 ± 1.45 m/s vs5.29 ± 0.67 m/s,P = 0.01) and (14.7 ± 8.1%vs9.36 ± 3.59%,P = 0.02)]. Patients had greater values of cIMT and LVMi than controls[(0.54 ± 0.06 mm vs 0.35 ± 0.12 mm, P = 0,00) and (32.4 ± 10.8 vs 28.8 ± 1.5,p = 0.01)].There was no difference in PWV, AIx, cIMT and LVMi values between with and without hypertension(P > 0.05). There was no significant difference in PWV values between with and without LVH(7.08 ± 1.9 m/s vs 6.08 ± 1.07 m/s, p = 0.12, respectively).Five patients had renal involvement. Although, all parameters were higher in patients with nephritis,weren’t statistically significant (P > 0.05).The mean SLEDAI score was10.1 ± 6.0 Among the patient group, all parameters significant correlations of moderate strength with disease duration and activity score(SLEDAI).Our results demonstrated that As might become apparent before morphologic changes, independent of hypertension,hyperlipidemia and nephritisin SLE.

Morphological changes were also seen in normotensive patients.Also functional and morphological changes in CVS were correlated with activity score in early stage of disease.Apart from these data, PWV, increased cIMT and LVH were correlated with disease duration.We consider that the prognosis of SLE is associated with CVD more than renal involvement.

PS3-SAT-114

Hemorrahgic and purulent cardiac tamponade due to systemic lupus erythematosus in a 9 year old boy

M. Fares¹, M. Hassoun¹, H. Fakhoury¹, F. Shatila¹, B. Aoun* ¹

¹Rafic Hariri University Hospital, Beirut, Lebanon

Although pericarditis and pericardial effusion are common cardiac complications of systemic lupus erythematosus (SLE), cardiac tamponade is considered an atypical primary presentation of the disease. We report a case of a 9 year old male previously healthy presenting for fatigue, fever, and exertional dyspnea. Physical exam showed pallor, elevated Jugular venous pressure and pulsus paradoxus sign. Chest X-ray showed pleural effusions and cardiomegaly. Cardiac sonography showed severe cardiac tamponade necessitating an urgent pericardiocentesis that revealed a hemorrhagic and purulent pericardial effusion. All common causes of hemorrhagic and purulent pericardial effusion were excluded. Investigations for SLE revealed high anti-double-stranded DNA. Moreover, infront of the heavy proteinuria (2 g/l) and hematuria a kidney biopsy was done showing Tubulointerstitial nephritis with mesangial hypercellularity. Child received 3 methylprednisolone pulses and was maintained on oral steroids (60 mg/m2/day). In conclusion patients with SLE might present with very unusual findings and such diagnosis must be excluded infront of multiorgan involvement.

PS3-SAT-115

Ureteropelvic junction obstruction in children: single-center experience

N. Cetin* ¹, B. Yildiz¹, N. Kural¹, B. Tokar², I. Sivrikoz³, N. Akcar⁴

¹Eskisehir Osmangazi University, Faculty of Medicine, Department of Pediatric Nephrology, Eskisehir, Turkey, ²Eskisehir Osmangazi University, Faculty of Medicine, Department of Pediatric Surgery, Eskisehir, Turkey, ³Eskisehir Osmangazi University, Faculty of Medicine, Department of Nuclear Medicine, Eskisehir, Turkey, ⁴Eskisehir Osmangazi University, Faculty of Medicine, Department of Radiology, Eskisehir, Turkey

Ureteropelvic junction obstruction (UPJO) is a principal cause of hydronephrosis and loss of renal function in children. The purpose of our study was to evaluate the outcome of UPJO in children. We retrospectively reviewed the medical records of 48 consecutive children with UPJO [19 girls (19.6%) and 29 boys (60.4%)]. We detect accompanying some renal anomalies in our patients: multicystic dysplastic kidney (n = 5, 10.4%), horseshoe kidney (n = 2, 4.2%), VUR (n = 1, 2.1%) and ureterovesical obstruction (n = 1, 2.1%). Renal pelvis AP diameters were spontaneously regressed in 23 (47.9%) patients with UPJO. We did not detect any spontaneously regression in 10 patients that they were following up with ultrasonography. Pyeloplasty procedures were done in patients who have renal AP diameters >30 mm, symptoms include flank pain and UTI and any diuretic response in DTPA (>20 minute T1/2). AP diameters were regressed in 16 (33.3%) operated patients. Regression ratios of AP diameters were 56.44% in these patients. Mean regression time were 10.23 ± 6.02 months. T1/2 in DTPA were higher in operated patients than those of non-operated patients (p = 0.038, r = 0.342). Baseline renal functions tests in DTPA were similar in patients with operated and non operated patients (p > 0.05). In conclusion, UPJO patients should be following up due to high rate of spontaneously regression of AP diameters and T1/2 time in DTPA seems to be useful for determination of pyeloplasty procedures in patients with UPJO.

PS3-SAT-123

Severe hematuria in a child with multiple renovascular anomalies of the left kidney and Haemophilia B

D. Milošević* ¹, E. Bilić², D. Batinić¹, R. Štern-Padovan³, D. Turudić¹, M. Poropat⁴

¹Department of nephrology, University of Zagreb Medical School, Children’s University Hospital, Zagreb, Croatia, ²Department of hematology and oncology, University of Zagreb Medical School, University Hospital Rebro, Zagreb, Croatia, ³Department of radiology, University of Zagreb Medical School, University Hospital Rebro, Zagreb, Croatia, ⁴Department of nuclear medicine, University of Zagreb Medical School, University Hospital Rebro, Zagreb, Croatia

Objectives and study: A child with Haemophila B, allergic to F IX medication and with plasma F IX inhibitors occasionally successfuly treated with Novoseven® (aFVIIr) was admitted in hospital with severe hematuria, urine clothing and fall of blood RBC counts.

Methods: Clinical studies, abdominal ultrasound (US), US Doppler renal blood vessels imaging, MSCT kidney angiography, renal scintigraphy with Tc-99m-MAG3, Tc-99m-DTPA and Tc-99m-DMSA.

Results: Treatment with Novoseven® with enhanced fluid parenteral intake completely reduced hematuria and stabilize RBC blood count. Repeated US kidney and Doppler imaging revealed after a few days unilateral enlargement of left kidney, pyelon dilatation and hyperechogenic inhomogenous content (pyelon clothing). MSCT kidney angiography revealed left kidney 3 independent passable arteries (one with irregular position) and 2 veins (one accessory) with no sign of thrombosis. Dinamic scintigraphy with deconvolution of renographic curves performed with MAG3 and DTPA find severe damaged left kidney. With DTPA we find afunctional renografic curve and with tubular radiopharmaceutical MAG3 renografic curve obstructed. After functional damaged secreted segment retention of activity in parenchyma in tubular cells but not in calyceal system was found. DMSA scintigraphy revealed the total decreased uptake of activity in tubular cells, predominantly in anterior part of the upper pole. Separate renal function with DMSA were left 27%/ and right 73% and are the same in scintigraphy with MAG3. Separate renal function determined with glomerular radiopharmaceutical DTPA were 8,7% left and 91,3% for right kidney.

Conclusion: Although severe life-threathening hematuria was successfully treated with Novoseven® (aFVIIr), complications associated with congenital multiple vascular anomalies resulted in severe renal damage. With tubular agens we find damage on the parenchymal level, with glomerular agens DTPA even worse, reflecting the predominantly damage of the vascular bed of glomerulus. Possible recovery remains uncertain (future control scintigraphy).

PS3-SAT-124

The role of kidney biopsy in diagnosis of renal parenchymal anomalies in children

D. Milošević* ¹, D. Batinić¹, M. Šćukanec-Špoljar², Lj. Nižić¹, K. Vrljičak¹

¹Department of nephrology, University of Zagreb Medical School, Children’s University Hospital, Zagreb, Croatia, ²Department of pathology, University of Zagreb Medical School, University Hospital Rebro, Zagreb, Croatia

Objectives and study: Congenital renal parencyhimal anomalies belong in a group of rare kidney diseases associated with the end stage renal failure. Usually presented on ultrasound as “small kidneys”, the diseases assume considerable diagnostic and care workup. We analysed the percentage of renal parenchymal anomalies among kidney biopsies in our population and importance of childen/parents life style recommendations.

Methods: A retrospective clinical analysis of kidney biopsies.

Results: During past 13 years we peformed 450 kidney biopsies at University Hospital Centre Zagreb and Rijeka in children aged 0–17 years (22.3% of both hospital kidney biopsies, adult patients included). Congenital kidney parenchymal anomalies were diagnosed in 15 children (3.3%). Nephronophtisis was found in 8 children (median age 8.8 years, infants 1/8), oligomeganephronia revealed in 7 (median age 5.6 years, infants 5/7), of whom one child has combined histological picture of oligomeganephonia/interstitial nephritis. All children suffered eventually from progressive renal faulure. In one family we suspect of hereditary type disease. Multiple anomalies can be found in children with both diseases, primarily in oligomeganephronia.

Conclusions: Early correct diagnosis enabled us to postpone end stage renal failure by children/parents life style consulting and parental genetic counselling for the future progeny.

PS3-SAT-128

Diuretic ultrasonography in the evaluation of hydronephrosis in children

Đ. Košuljandić-Vukić* ¹, M. Saraga¹

¹Clinical Hospital Split, Department of Pediatrics, Split, Croatia

Objectives of the study: Diuretic ultrasonography (DUS), diuretic urography (DUR) and diuretic renography (DREN) are functional diagnostic methods used to differentiate obstructive from non-obstructive hydronephrosis and to assess degree of obstruction. These methods are widely used in clinical practice, sometimes with doubtful results. The aim of this study was to determine accordance and reliability of DUS and DUR in relation to DREN as a method of choice.

Patients and methods: We analyzed 87 children with hydronephrosis (97 renal units) through 11-year long retrospective study. In all children, ultrasonography and DREN were done. DUS was performed in 50 and DUR in 39 children. Following furosemide administration, urine wash out (WO) from kidney pyelo caliceal system was analyzed according to the three grades (normal, partial obstruction and obstruction) after DUR and DUS in relation to WO after DREN.

Results: We found a statistically significant correlation between the WO after DREN in relation to the categories of WO in DUR (χ2 = 7.8; P = 0.02) and in DUS (χ2 = 9.2; p = 0.010). DUR and DUS discriminated obstruction and normal WO (z = 2.38; p = 0.017 for DUR and z = 2.74; p = 0.005 for DUS). DUR and DUS also discriminated obstruction from partial obstruction in relation to DREN (z = 2.1; p = 0.035 for DUR and z = 2.44; p = 0.014 for DUS). We did not find that DUR and DUS discriminate normal from partial wash out (z = 1.47; p = 0.14 for DUR and z = 1.013; p = 0.322 for DUS). DUS showed sensitivity of 68%, specificity of 69%, positive predictive value of 86%, negative predictive value of 43% and accuracy of 68%.

Conclusion: DUS and DUR are good functional methods to diagnose obstruction with relatively good positive predictive value, but poor negative predictive value. DUS is simple method bearing no x-ray burden which may be repeatedly used in diagnostic work-up of hydronephrosis.

PS3-SAT-129

Kidney injuries in children with different cystitis types.

E. Aleksentseva* ¹, V.P. Sitnikova¹, A.P. Shvyrev¹, T.G. Zvyagina¹

¹Voronezh Medical Academy, Voronezh, Russian Federation

Objectives and study: To detected the kidney changes affected by pyelonephritis with different types of cystitis. We investigated 22 girls in Nephrology Department of Voronezh Region Children’s Hospital of the age 4–17 years. According to previous cystoscopy catarrhal cystitis was detected in 11 (50%) patients and cystic cystitis—in 11(50%) children.

Methods: The main criteria for the detection of kidney injury were: urea in serum, plasma creatinine level, glomerular filtration rate, and proteinuria. Urine specific gravity was defined during conducting dry diet.

Results: Patients with cystic cystitis had leukocyturia: 523.0 ± 61.2*106/l, proteinuria: 0.22 ± 1.34 g/l, bacteriuria: 900.0 ± 106.2*105/ml, maximum urine specific gravity: 1020.0 ± 3.8, urea in serum: 4.3 ± 1.3 mmol/l, plasma creatinine level: 0.7 ± 0.1 mg/dl.

Group of patients with cattharal cystitis had leukocyturia: 30.9 ± 2.4*106/l, proteinuria: 0.027 ± 1.32 g/l, bacteriuria: 500.0 ±58.4 105/ml, maximum urine specific gravity: 1028.0 ± 3.8, urea in serum: 3.6 ±1.0 mmol/l, plasma creatinine level: 0.6 ± 0.1 mg/dl. Conducting comparative analysis of laboratory parameters showed that patient with cystic cystitis had significantly higher proteinuria (p < 0.01), bacteriuria (p < 0.05) and leukocyturia (p < 0.02) then the patients with cattharal cystitis. Urine specific gravity in patients with cystic cystitis was lower (p < 0.05) then the patients with cattharal cystitis. The level of plasma creatinine and urea in serum as well as glomerular filtrate rate (108.0 ± 10.0 ml/min) were the same in two groups.

Conclusion: The type of cystitis might influence on kidney’s injury (damage) in children.

PS3-SAT-149

Arterial stiffness and body composition in children with cystic fibrosis

T. Buehler¹, S. Tschumi¹, B.S. Bucher¹, N. Regamey², C. Casaulta², M.H. Schoeni², G.D. Simonetti* ¹

¹Division of pediatric nephrology, University Children\’s Hospital, Inselspital, Bern, Switzerland, ²Division of pediatric pneumology, University Children\’s Hospital, Inselspital, Bern, Switzerland

Objectives and study: Increased arterial stiffness is an independent risk factor for cardiovascular disease. It occurs in inflammatory diseases indicating an ageing of the vasculature. In the present study we aimed to assess arterial stiffness and body composition in children with cystic fibrosis (CF).

Methods: Digital volume pulse analysis, with the computation of the stiffness index (SI) and pulse wave velocity between carotid and femoral artery (PWVcf), were determined in 31 CF children (13 female, median age 12.2 ± 3.2) and in 48 healthy children, matched for age and gender. Body composition was assessed using a bioimpedance spectroscopy device (BCM-Monitor, FMC). Lean and fat mass were expressed by the Lean Tissue Index (LTI) and the Fat Tissue Index (FTI), and the hydration status as ‘fluid excess’ relative to the fluid content of healthy children (Reference data from 607 healthy children).

Results: SI and PWV, corrected for age or height, were significantly higher (1.22 ± 031 SI SDS vs. 1.0 ± 0.15 SI SDS, p < 0.0001 and 1.9 ± 1.3 PWV SDS vs. 1.3 ± 1.0 PWV SDS, p = 0.02) in CF children compared to controls. Mean LTI was 13.7 ± 2.0 kg/m² and mean FTI was 3.6 ± 2.4 kg/m²; 20% of the CF children showed a reduced lean mass, however the fat mass was similar to controls. PWV was increased in CF children positive for Pseudomonas aeruginosa or Stenotrophomonas maltophilia (6.8 ± 1.6 vs. 5.7 ± 0.7, p = 0.003) compared to the non-infected ones.

Conclusions: SI and PWV, indicating central arterial stiffness is increased in children with CF. Arterial stiffness in children with CF seems to be associated with Pseudomonas aeruginosa or Stenotrophomonas maltophilia colonization. Normal fat tissue distribution and reduced lean tissue are characteristics of children with CF. These findings have important implications for the management of cardiovascular functions in patients with CF and require further exploration so that cardiovascular health can be maintained.

PS3-SAT-151

Neurofibromatosis type 1 as an example of high prevalence of secondary hypertension

M. D’Arco¹, G. Pellino¹, S. Guarino¹, A. La Marca¹, R. Pizza¹, S. Strianese¹, G. Lama* ¹

¹Second University of Naples, Naples, Italy

Objectives and studies: The aim of this retrospective study is to assess the prevalence of hypertension in a population of 69 pediatric patients with NF1 and to confirm the relationship between NF1 and secondary form of hypertension.

Methods: In the Pediatric Centre NF1 of the Second University of Naples we take care of 312 patients. We checked blood pressure with Office Monitoring Method (OBPM) and then we performed ABPM on 69 patients (36 males and 33 females) with a medium(mean) age of 11 years (5–25 years). We considered hypertensive patients who showed two ABPM with mean SBP24-h and/or mean DBP24-h above age and sex specific 95th percentile.

Diagnosis of renovascular hypertension is suspected in patients with poorly controlled blood pressure on at least two antihypertensive agents and confirmed by PRA-ALDO, echo-color Doppler of the renal artery and \“pulse wave velocity test”, Renal scintigraphy performed before and after administration of an angiotensin-converting enzyme inhibitor, MR angiography of renal artery and DSA . The urinary assay of catecholamines, VMA, 5-HIAA, HVA and metanephrines can verify diagnosis of pheochromocytoma. Aortic coarctation can be confirmed by chest Rx, echo-color-Doppler and MR Angiography.

Results: Hypertension was diagnosed in 14 patients, with a medium age of 10 years and 4 months (5–14 years) at the time of diagnosis. Results: suspected renovascular hypertention in 2 patients at present in therapy with two drugs, bilateral renal artery stenosis in one patient, pheochromocytoma in 3 patients, aortic coarctation in one patient and essential hypertension with abnormalities of the course of both renal arteries in one patient. Six patients were lost during the follow-up.

Conclusions: The prevalence of Hypertension in the NF1 patients is 20,29% and the prevalence of secondary hypertension is 87.5%.

PS3-SAT-155

Risk of urinary tract infection in children under two years of age with postnatally detected hydronephrosis

H. Flögelova* ¹, J. Halek², O. Šmakal³, K. Michalkova⁴, V. Švecova⁴

¹University Hospital Olomouc, Department of Paediatrics, Olomouc, Czech Republic, ²University Hospital Olomouc, Department of Neonatology, Olomouc, Czech Republic, ³University Hospital Olomouc, Department of Urology, Olomouc, Czech Republic, ⁴University Hospital Olomouc, Department of Radiology, Olomouc, Czech Republic

Objectives and study: The objective was to find out if children with renal pelvis dilatation(PD)detected by postnatal ultrasound (US) screening have higher incidence of febrile urinary tract infection (UTI) in the first two years of life than those with normal US findings.

Methods: Prospective US examinations of the kidneys were performed in all 6,088 mature newborns born in the University Hospital Olomouc in the period 2005–2008. All infants with PD ≥5 mm in the transverse anteroposterior intrarenal (APIR) view were followed. This group of 236 children was divided into 4 subgroups according to the extent of PD: 5–7 mm, 7–10 mm, 10–15 mm and ≥15 mm. The incidence rates of febrile UTI, obstructive uropathy and vesicoureteral reflux were studied. Retrospectively, all the remaining infants (5,852 children with normal US findings) were evaluated for both inpatient and outpatient treatment of febrile UTI in the first two years of life. Fisher’s exact test and chi-square test were used for statistical analysis.

Results: The incidence of febrile UTI in infants with normal kidney US findings was 1.2%. Children with postnatally detected renal PD had statistically significantly higher rates of febrile UTI, both generally (8.90%, p < 0.0001) and in all subgroups with the exception of the greatest dilatation subgroup. Febrile UTI developed in 7.53% with APIR 5–7 mm (p < 0.0001), 8.57% with APIR 7–10 mm (p = 0.001), 20% with APIR 10–15 mm (p = 0.003) and 6.67% with APIR ≥15 mm (p = 0.238, nonsignificant difference).

Conclusions: The incidence of febrile UTI was 7 times higher in infants with postnatally detected hydronephrosis than in those with normal postnatal kidney US findings. The differences were statistically significant in 5–15 mm renal pelvis dilatation.

PS3-SAT-160

Vitamin D receptor gene polymorphism in children with urinary tract infecion

I. Akil* ¹, S. Aslan¹, G. Aslan², H. Onay², B. Ozyurt³, F. Ozkinay²

¹Celal Bayar University, Dept. of Pediatric Nephrology, Manisa, Turkey, ²Ege University, Department of Genetics, Manisa, Turkey, ³Celal Bayar University, Dept. of Public Health, Manisa, Turkey

It is known that small alterations leading to some VDR alleles affect resistance or susceptibility to infections. In this study it is aimed to examine VDR gene polymorphisms in urinary tract infection (UTI), which is common and cause of important morbidity in children, and in renal scar formation due to this.

92 patients diagnosed as UTI and 105 children without history of UTI before as a control group were evaluated. The VDR gene BsmI, FokI, ApaI and TaqI polymorphisms were evaluated in both patients and control groups.

BsmI polymorphism genotype distribution was similar between patient and control groups. There was a significant difference between patient and control groups in FokI polymorphism (p = 0 < 001) In ff genotype risk of UTI was significantly increased (p < 0.01) and the risk was 3,94 times higher (OR = 3,94; %95 CI 1,71–9,09). ApaI polymorphism was significantly increased in control group (p < 0.01) and evaluated as a protective factor. In comparison of TaqI genotype between patient and control groups there was no statistically significant difference but in both Tt and tt genotypes there was minimal increased risk of UTI.

Results of this study suggest that VDR gene polymorphism can be important for susceptibility to UTI and renal scar formation. Associations between VDR polymorphisms and UTI is in accordance with the knowledge of vitamin D modulates immune response against infections.

PS3-SAT-163

Skin autofluorescence (sAF) as a new noninvasive marker of cardiovascular damage in children with end-stage kidney disease (ESKD)

I. Makulska* ¹, M. Szczepańska², D. Drożdż³, D. Zwolińska¹

¹Department of Pediatric Nephrology, Wrocław Medical University, Wrocław, Poland, ²Dialysis Unit, Silesian Medical University, Zabrze, Poland, ³Dialysis Unit, Children’s Hospital, Jagiellonian University, Cracow, Poland

Introduction and aims: Advanced glycation endproducts (AGEs) may contribute to inflammatory processes, endothelial dysfunction and cardiovascular damage resulting in the development and progression of atherosclerosis in ESKD population. It has been shown that sAF (marker of the AGEs skin concentration) is strongly associated with arterial stiffness and mortality in hemodialyzed adults, independently of traditional risk factors. The aim of the study was to determine, for the first time in children, whether sAF is increased and related to novel markers of endothelial dysfunction, structural and functional cardiovascular changes.

Methods: 20 children (12 boys and 8 girls), mean age 14,3 ± 2,3 years on peritoneal dialysis (PD) and 20 children (10 boys and 10 girls), mean age 15,0 ± 3,3 on hemodialysis (HD) were included in the study and compared to 26 healthy age-matched subjects. We evaluated sAF using AGE-Reader. Structural and functional cardiovascular changes were measured as intima–media thickness (IMT) of the carotid artery, arterial pulse wave velocity (PWV) and left ventricular mass index (LVMI). Serum sE-selectin, MMP-9, TIMP-1, ADMA and SDMA were measured by ELISA method.

Results: sAF, cIMT, PWV/ht, LVMI, sE-selectin, MMP-9, TIMP-1, ADMA and SDMA were significantly higher in dialysed patients vs controls (p < 0,0001). A significant positive correlation was shown between sAF and PWV/ht (p = 0,03), LVMI (p = 0,0001), ADMA (p < 0,001), SDMA (p = 0,0009), MMP-9 (p < 0,001), TIMP-1 (p = 0,04). A significant positive correlation was observed between cIMT and PWV/ht (p = 0,03), as well as sE-selectin (p < 0,001). In the multiple regression analysis LVMI (p = 0,005), sE-selectin (p = 0,03) and MMP-9 (p < 0,001) were independent predictors of the sAF.

Conclusions: In ESKD children the accumulation of tissue AGEs occur. A significant association between sAF and investigated markers of endothelial and cardiovascular status supports a role for AGEs as a contributor to vascular damage and shows that sAF may be a good, easily applicable tool for assessing the risk of atherosclerosis development and cardiovascular events in ESKD children.

PS3-SAT-164

The role of oxidative stress in renal scar formation due to primary vesicoureteral reflux

S. Kose¹, R. Dusunsel², M. H. Poyrazoglu², Z. Gunduz², K. Kose³, F. Bastug², S. Tulpar², D.B. Keti³, S. Yel², I. Dursun* ²

¹Erciyes University Faculty of Medicine, Department of Pediatrics, Kayseri, Turkey, ²Erciyes University Faculty of Medicine, Department of Pediatric Nephrology, Kayseri, Turkey, ³Erciyes University Faculty of Medicine, Department of Biochemistry, Kayseri, Turkey

The aim: To evaluate the role of oxidative stress in renal scar formation due to primary VUR. The study consisted of 44 patients (11 boys, 33 girls) who were diagnosed as primary VUR [32 renal scar (+) and 12 renal scar (−) with DMSA]. Eighteen healthy subjects appropriate with age, were included as controls in the study. The patients were divided into 3 groups according to the reflux grade in VCUG as grade I–II, grade III and grade IV–V. During the study all patients were sterile for urine analysis. Blood samples were taken at the admission and myeloperoxidase (MPO) activity, advanced oxidation protein products (AOPP), lipid hydroperoxides, pyrrolized proteins and thiol levels were measured from the plasma and serum samples.

Results: MPO activity, AOPP, pyrrolized proteins and lipid hydroperoxides levels were significantly higher in VUR group than control group and there was no significant difference between thiol levels. There was no significant difference between MPO activity, AOPP, pyrrolized proteins, lipid hydroperoxides and thiol levels in scar (+) and scar (−) groups. MPO activity, AOPP, pyrrolized proteins and lipid hydroperoxides levels were significantly higher in scar (+) and scar (−) group when compared with control group. There was no significant difference between MPO activity, AOPP, pyrrolized proteins, lipid hydroperoxides and thiol levels in mild, moderate and severe reflux groups. MPO activity, AOPP, pyrrolized proteins and lipid hydroperoxides levels were significantly higher in all reflux groups when compared with control group.

Conclusion: High levels of oxidative stress markers in patients with VUR were found to be related to VUR, independently from renal scar and reflux grade.

PS3-SAT-167

Urodynamic findings in children with vesicoureteral reflux after three years of age

I. Palcic* ¹, H. Strizic², A. Cvitkovic Roic³

¹University Hospital Center “Sestre Milosrdnice”, Children’s Hospital Zagreb, Zagreb, Croatia, ²Health facility Zagreb Center, Zagreb, Croatia, ³Polyclinic for pediatric diseases Helena, Zagreb, Croatia

Objectives: It is well known that lower urinary tract dysfunction plays significant role in pathogenesis of secondary vesicoureteral reflux (VUR) and that bladder dysfunction is a negative prognostic factor for spontaneous resolution of primary VUR. Aim of our study was to evaluate urodynamic findings in children who had VUR after three years of age with or without symptoms of voiding dysfunction.

Methods: We included 92 children in this retrospective study, 78 girls and 14 boys, with persistent or newly diagnosed VUR after three years of age. All children underwent urodynamic investigations, regardless of whether they had symptoms of voiding dysfunction.

Results: The mean age at the time of urodynamic evaluation was 6,15 years. (SD 2,5). 81 patients (88%) had urinary tract infections and 49 patients (53%) had symptoms of voiding dysfunction (urge or incontinence), based on the clinical history. Pathological urodynamics were found in 62 (67,4% of the total examined children) of which detrussor hyperactivity in 44 (71% of children with pathological urodynamics) and dysfunctional voiding in 18 (29,%). In 41 of all children (44,6%), urinary tract infections were the only symptom. Even 22 of them (53,6%) had pathological urodynamic study findings, although they had no symptoms of voiding dysfunction.

Conclusion: Our study confirmed that in children with VUR after three years of age, urodynamic study should be performed in order to exclude lower urinary tract dysfunction even in children without any symptoms of voiding dysfunction. The therapy of VUR should be planed according to the urodynamic study findings.

PS3-SAT-168

Applicability of more selective imaging program in children diagnosed with a first urinary tract infection

I. Butorac-Ahel* ¹, S. Flajšman-Raspot¹, M. Šubat-Dežulović¹

¹Department of Pediatrics, Clinical Hospital Centre Rijeka, Croatia

Introduction: Urinary tract infection (UTI) in common during the childhood. Beside reached consensus on promt antibiotic treatment of UTI, imaging program in children with a first febrile UTI still remains controversal.

Aim of our study was to evaluate the applicability of a more selective imaging program as recomended by The National institute for Health and Clinical Excellence (NICE) guidlines for management of UTI in children.

Patients and methods: A retrospective study was conducted from January 2009 to July 2010 of children diagnosed with a first febrile UTI classified as typical or atypical UTI. All children underwent renal ulatrasound (US) within 3 days followed by voiding cystouretrogram and acute DMSA scans up to 10 days after the diagnosis of UTI.

Results: Of 195 chidlren (M 68, F 127) retrospectively reviewed, mean age 1.91 years (range 0–17 years), typical UTI had 154 and atypical UTI had 41 patients. Structural anomalies detected by US had 21 (13.6%) with typical and 41 (17%) patients with atypical UTI (p = 0.7). Parenchymal changes detected by US with typical versus atypical UTI had 68 (44%) and 20 (49%) patients, respectively. Acute DMSA scans revelied ≥2 focal lesions in 56% with decreased differential function (<45%) in 16.4% of patients. VUR was diagnosed in 44 (22.7%) patients equally distributed between typical and atypical UTI, while 3 patients with atypical UTI had hydronephrosis. If the NICE UTI guidlines had been followed, in total 34 refluxing ureters and 24 kidneys with parenchymal lesions would have not been diagnosed.

Conclusions: Since a significant number of structural and parenchymal changes were diagnosed by US, we consider US to remain obligatory imaging procedure in all children with a first febrile UTI. In children older than 3 years, US should be followed by acute DMSA scan prior to VCUG.

PS3-SAT-171

Papillorenal syndrome associated with a deletion on chromosome 10

J. Hoefele* ¹, E. Kunstmann², I. Rost¹, H. G. Klein¹, M. Gabert¹, U. Heinrich¹

¹Center for Human Genetics and Laboratory Medicine Dr. Klein and Dr. Rost, Martinsried, Germany, ²Institute of Human Genetics, Julius-Maximilians-University, Würzburg, Germany

Papillorenal syndrome, also called renal coloboma syndrome (RCS), is an autosomal dominant inherited disease characterized by renal hypoplasia and developmental abnormalities of the optic nerve ranging from mild optic disc dysplasia to optic nerve aplasia. Additional anomalies may include vesicoureteric reflux, sensorineural deafness, and skin abnormalities with variable penetrance. Mutations in the PAX2 gene have been identified causing RCS.

Here we report a boy, who was diagnosed directly after birth with cheilognathopalatoschisis, pendular nystagmus, and talipes calcaneus. Ultrasound examination revealed a bilateral renal dysplasia with vesicoureteral reflux. Within the following months the patient showed a mild mental retardation. Magnetic resonance imaging of the brain demonstrated a partial agenesis of the corpus callosum, small nervi optici, and the absence of the optic chiasm consistent with a septooptic dysplasia. DNA sequence analysis of the PAX2 gene did not show any mutation. The following CGH-array demonstrated an interstitial deletion of the long arm of chromosome 10 [arr 10q24.2q24.32(99,938,259-103,712,193)x1]. The deletion spanning 3.77 Mb contained 44 known genes. Among these genes, PAX2 seemed most likely to be responsible for the clinical spectrum of the patient\’s RCS symptoms.

To date, only two patients have been reported with a PAX2 gene deletion and the clinical signs of RCS. Our findings suggest that: i) PAX2 deletion testing should be performed additional to DNA sequence analysis in RCS patients, who tested negative for PAX2 mutations, and ii) a large number of undiagnosed cases may exist.

PS3-SAT-173

“in vitro” effectiveness of probiotics on E. coli in comparison with commonly used antibiotics in treatment of urinary tract infections in children

K. Meštrović Popovič* ¹, N. Marčun Varda², A. Cencič³,⁴, M. Txopitea Ander³, M. Eneko³, M. Gorenjak⁴, L. Gradišnik⁴

¹General Hospital Celje, Department of Paediatrics, Celje, Slivenia, ²Medical Centre Maribor, Department of Paediatrics, Maribor, Slovenia, ³University of Maribor, Faculty of Agriculture and Life Sciences, Maribor, Slovenia, ⁴University of Maribor, Faculty of Medicine, Maribor, Slovenia

Objectives and study: Management of recurrent urinary tract infections (UTI) with antibiotic prophylaxis is well defined. Because of rising resistance of bacteria to antibiotics, questionable cost/effectiveness and parental dissaproval of long term antibiotic prophylaxis, better options are looked for. One of the expanding areas of research is possible preventive role of probiotics. The aim of our study was to determine the inhibitory effect of some probiotics vs. antibiotics on E. coli in preclinical study. Probiotic with the best inhibitory results will be used in future clinical trial.

Methods: Clinical isolates of E. coli and a control E. coli strain (ATCC 11105) were tested for inhibition by probiotic strains and some antibiotics using well diffusion method. We used L. plantarum strains (PCS20, PCS22, PCS25, PCS26) from Slovenian local cheese and 3 commercial probiotics (Probio Junior, Prolife and BioGaia) in comparison to the widely used L. rhamnosus LGG strain (“the golden standard”). We also tested gentamycin (40 mg/ml) and cefuroxime (100 mg/ml), two commonly used antibiotics in treatment of UTI.

Results: We found out that all probiotics have lower activity against E. coli (approximately 30% less) than both antibiotics, cefuroxime and gentamycin. Most of the tested probiotic strains exert resembling activity against uropathogenic E. coli. Prolife in yeast potato dextrose broth, encouraging growth of yeasts, in this case Saccharomyces cerevisae, produced significant inhibition of growth of most E. coli strains, especially the ATCC control strain, and isolate 6497. Such activity was comparable to that of gentamycin, but significantly lower than that of cefuroxime.

Conclusions: Antimicrobial effects of some probiotics on E. coli clinical strains show promissing results for possible prevention of UTI. Although Saccharomyces cerevisae showed very good results, we believe that yeasts as possible opportunistic pathogens should not be used in clinical practice. However, further validation is necessary.

PS3-SAT-176

Anomalies of the urinary system in rare dysmorphic syndromes.

K. Fornalczyk* ¹, K. Kilis-Pstrusinska¹, R. Smigiel², M. Sasiadek², D. Zwolińska¹

¹Dept. of Paediatric Nephrology, Wroclaw Medical University, Poland, ²Genetics Departament, Wroclaw Medical University, Poland

Urinary system anomalies (USA) usually present as isolated malformations, although can also coexist with multiple congenital abnormalities. The diagnosis of USA made in the early childhood can improve the prognosis in children affected with dysmorphic syndromes. Between the years 2007 and 2010, seven children with multiple congenital anomalies were hospitalized in our Department, among them: 2 children with Wolf- Hirschorn syndrome (WHS), 2 with Bardet-Biedel syndrome (BBS), 1 child with Beckwith-Wiedemann syndrome (BWS), 1 with Joubert syndrome (JS) and 1 with VATER association.

The aim of the study was to analyze the type of USA and course of kidney disease in children with rare dysmorphic syndromes regarding to their clinical manifestation and genetic background. The following data were included in the study: time of diagnosis of genetic disorder, type of underlying mutation, first symptoms and time of diagnosis of USA, type of USA, stage of chronic kidney disease (CKD), treatment, other associated disorders and coexisting therapeutic problems. Five children were diagnosed with an impaired kidney function in the neonatal period. Following anomalies were found: BBS—multicystic dysplastic kidneys, WHS—agenesis of the left kidney, multicystic dysplastic kidney, grade III/IV right vesicoureteral reflux (VUR), WHS—multicystic dysplastic kidney, JS—multicystic dysplastic kidney, VATER association -agenesis of right kidney, grade V left VUR. In other children USA were detected in early infancy: BBS—multicystic dysplastic kidney, grade III left VUR, BWS—spongious kidneys. Renal replacement therapy has been introduced in four children, among them one child has been on dialysis from the first days after the birth. In the remained patients CKD stage II–III (eGFR 35–70 ml/min/1.73 m²) was recognized. In children with dysmorphic syndromes and associated USA chronic kidney disease remains one of the most important prognostic factors for survival and quality of life.

PS3-SAT-177

OEIS complex—report of two cases

K. Vrljičak* ¹, R. Grizelj², T. Luetić³, D. Batinić¹

¹Division of Nephrology, Department of Pediatrics, University Hospital Centre Zagreb, Zagreb, Croatia, ²Neonatal Intensive Care Unit, Department of Pediatrics, University Hospital Centre Zagreb, Zagreb, Croatia, ³Division of Pediatric Surgery and Urology, Department of Surgery, University Hospital Centre Zagreb, Zagreb, Croatia

Objectives and study: Exstrophy of the cloaca, often referred as OEIS complex (omphalocele, exstrophy, imperforate anus and spinal defects) is the most severe end of the spectrum of the exstrophy-epispadias complex.

Methods and results: We report two infants with OEIS complex. Parents are healthy and non-consanguineous. Family history is unremarkable. Surgery was performed on fourth and first day of life respectively.

First patient: The postdelivery examination showed cloacal exstrophy with large bladder halves and ureteral orifices bilaterally, terminal ileum protruding between the bladder halves and a small opening of the blind-ending foreshortened hindgut on the left, small and bifid penis with adjacent scrotum on each side. He had an omphalocele and imperforate anus. Renal ultrasound was normal. X-ray revealed hemivertebrae in the thoracic spine and widely separated pubic symphysis.

Second patient: It was a twin pregnancy. Prenatal ultrasound revealed one already lost twin, an omphalocele and right hydronephrosis. On examination, there was an cloacal exstrophy, a bifid clitoris and a single perineal opening that drained into a common cloaca with a vaginal halves located on each side. Scintigraphy showed horseshoe kidney and hydronephrosis. X-ray revealed cervical spine alordosis, hypoplastic C4 and lower thoracic and lumbar vertebral malformations.

Conclusions: Incidence of the OEIS complex is 0.5–1/200.000 live births. The underlying cause remains unknown. Blood samples were sent for a genetic analysis. Prenatal diagnosis should lead to parental counseling. The aims of surgical management include abdominal wall closure, prevention of short bowel syndrome, provision of fecal and urinary continence, preservation of renal function and reconstruction of functional and cosmetically acceptable genitalia. The success of these procedures cannot guarantee a good quality of life. The survivors have long-term psychosexual developmental difficulties and require life-long follow-up from a multidisciplinary team of experts.

PS3-SAT-187

Renal phenotype-genotype correlations in Beckwith Wiedeman syndrome

L. Peruzzi* ¹, A. Mussa², R. Camilla¹, R. Gallo¹, D. Melis³, G. Baldassarre², A. Amore¹, G. Battista Ferrero², R. Coppo¹

¹Nephrology Dialysis Transplant Regina Margherita Children’s Hospital, Turin, Italy, ²Department of Pediatrics, University of Turin, Turin, Italy, ³Department of Paediatrics, “Federico II” University, Naples, Italy

Objectives and study: Beckwith-Wiedemann syndrome (BWS,OMIM #130650) is a somatic overgrowth condition with several congenital abnormalities, including renal malformations. In 75% of cases it is due to derangements on 11p15.5: on Imprinting center 1 (IC1) (regulating the expression of insulin growth factor 2 (IGF2) and tumor suppressor gene H19) or imprinting center 2 (IC2) (regulating the expression of cyclin-dependent kinase inhibitor 1C and other genes). Both IC are differentially methylated and only one parental allele is normally expressed. The most frequent anomalies are loss of methylation (LOM) of IC2 on maternal chromosome, gain of methylation (GOM) of IC1 on maternal chromosome or both LOM-IC2 plus GOM-IC1 caused by paternal uniparental disomy for chromosome 11 (UPD), or mutations in the CDKN1C allele. No systematic studies were addressed to the renal aspect of the syndrome and genotype-phenotype correlations are lacking. Aim of this study was to define renal phenotype-genotype correlations in a cohort of 67 genetically characterized BWS patients.

Methods: Imaging and laboratory studies performed in 67 BWS patients were retrospectively reviewed and matched with the respective molecular pattern detected by specific analysis of the methylation pattern of the 11p15.5 region.

Results: 38 (56.7%) patients had a total of 64 nonmalignant kidney/urinary tract anomalies: nephromegaly (24), renal collecting system abnormalities (14), cryptorchidism (11), nephrocalcinosis/nephrolithiasis (5), cysts (5), and dysplasia (1). 4 had Wilms’ tumor and renal hyperplasia. Renal anomlies were almost constant in the BWSIC1 group, with nephromegaly in 100% and collecting system abnormalities in 50%. BWSUPD and negative patients had also frequent anomalies (63.6% and 61.9%, respectively); only 36.0% of BWSIC2 had renal anomalies (p = 0.003). Cryptorchidism was associated with major abdominal wall defects (p < 0.001) and more frequent in the BWSIC2 subgroup (p = 0.028).

Conclusions: Our BWS cohort displayed renal defects in 55.5% of cases. Nephromegaly was the most frequent finding, associated with IC1 imprinting defects and Wilms tumor.

PS3-SAT-191

Do parents of enuretic children take care of them like they did 20 years ago?

L. M. Rodríguez* ¹, E. Taborga², S. Lapeña¹, V. Martínez², J. M. Marugán³, A. Cobo², M.Fernández¹

¹Unidad de Nefrología Pediátrica, Servicio de Pediatría, Complejo Asistencial Universitario de León (CAULE), León, Spain ²Pediatría, Atención Primaria, Gijón. Asturias, ³Servicio de Pediatría, Hospital Clínico Universitario de Valladolid, Valladolid, Spain

Objective: To find out if the care given to enuretic children by their parents in our context has changed in the last 20 years.

Patients and methods: We compared the answers to a questionnaire administered to 171 and 102 parents respectively in 1989 and 2009 whose children were selected through a survey conducted in their schools. The survey questions, included below, were designed to assess any possible changes in the way in which parents care for children who suffer this condition.

• Do you consider enuresis a disease?

• Do you chide your child in case of a bedwetting event?

• Have you visited the doctor with your child to consult about this condition?

• Have you tried any type of treatment for your child\’s problem?

• Have you treated your child with medications?

• Have you tried enuresis alarms?

The results of the surveys, administered 20 years apart, were compared using a chi-square test.

Results:

Year 1989 Year 2009 p-value

Parents:

• Consider enuresis a disease

108/171 31/102 0.0000

• Chide children in case of a bedwetting event

16/171 8/102 ns

• Have visited the doctor with their children

69/171 80/102 0.0000

Their children:

• Have undergone some type of treatment

68/171 28/102 ns

• Have used medication

10/171 12/102 ns

• Have used an enuresis alarm

9/171 1/102 ns

Conclusions: In our context, enuresis is no longer perceived as a disease by most parents, probably as a result of the information that they receive from their children\’s doctor, whom the visit more regularly. However, as it was the case 20 years ago, only about one third of enuretic children undergo some type of treatment. Medications are not frequently used and enuresis alarms, only very occasionally. Chide children when bedwetting happens is a very infrequent practice.

PS3-SAT-193

Differences in renal function in three morphological anomalies that occur with severe dilation of the urinary tract in children

M. Monge* ¹, I. Abreu-Yanes¹, V. García-Rodríguez¹, S. González-Cerrato¹, M. I. Luis-Yanes¹, F. Claverie-Martín¹, V. García-Nieto¹

¹Hospital Nuestra Señora de Candelaria, Pediatric Nephrology Unit, Santa Cruz de Tenerife, Spain

Introduction: Severe dilation of the urinary tract in children is usually caused by ureteropelvic junction obstruction (UPJO) or vesicoureteral reflux (VUR). However, there are children with hydronephrosis in which no associated malformation is detected (primary hydronephrosis, PH). We studied whether there are differences in the behaviour of renal function in children with these three types of morphological anomalies.

Patients and methods: We included 38 children (30M, 8F) diagnosed of UPJO (n = 12), VUR (n = 8) and PH (n = 18). Everyone had a transverse diameter of the pelvis of no less than 2 cm. At diagnosis, we determined the maximum urine osmolality with desmopressin stimulus (Uosm) and the ratio albumin/creatinine (Alb/Cr) to all patients and the ratio of NAG/creatinine (NAG/Cr) to 30 of them. All patients had a cystogram performed and renogram with furosemide.

Results: Uosm was reduced in 100% of cases of VUR, in 75% of UPJO and in 16.7% of PH. Alb/Cr was elevated in 62.5% of cases of VUR in 8.3% of UPJO and 11.1% of PH. NAG/Cr was increased in 42.8% of cases of VUR, in 25% of UPJO and 6.7% of PH. Differences between groups were tested for both Uosm values (ANOVA, p < 0.001) and for Alb/Cr and NAG/Cr (Kruskal-Wallis, p = 0.02 and 0.008, respectively).

Conclusions: Uosm is the most sensitive test to detect impaired renal function in cases of overpressure in the urinary tract. Urinary albumin is elevated especially in cases of VUR. Urinary NAG is a marker of overpressure less sensitive than Uosm. In cases of PH, renal function is altered slightly.

PS3-SAT-195

Albumin urinary excretion is preferently a hyperfiltration marker in children with vesicoureteral reflux

M.I. Luis-Yanes* ¹, L. Martín-Conde¹, M.I. Hernández-Sanjuán¹, J.R. Alberto-Alonso¹, M.J. Hernández-González¹, L. Anton², V. García-Nieto¹

¹Hospital Nuestra Señora de Candelaria, Pediatric Nephrology Unit, Santa Cruz de Tenerife, Spain, ¹Hospital Nuestra Señora de Candelaria, Pediatric Surgery Unit, Santa Cruz de Tenerife, Spain

Introduction: An increased urinary albumin (Alb) excretion is an early marker for glomerular injury in diseases with renal hyperfiltration such as diabetic nephropathy or in the case of renal parenchyma loss. In adition, Alb is recognized to be a marker for endotelial damage. Nowadays, however, it is not know if the Alb can be increased in diseases with overpressure in the urinary tract.

Patients and methods: In a retrospective longitudinal study we included 51 children (26M, 25F) who had been diagnosed of VUR by voiding cystourethrography (VCUG) and who had two Alb/creatinine (Alb/Cr) determinations and two scintigraphies (DMSA), one at diagnostic time (T1) and other after VUR correction (T2). Specimens for Alb/Cr determinations were collected in all patients without fever when they suffered pyelonephritis.

Results: At T1 10 out of 51 (19.6%) exhibited an increased Alb/Cr ratio [loss of renal parenchyma (n = 4); post acute pyelonefritis (n = 4; 2 VUR grade III, 1 VUR grade IV, 1 VUR grade V); normal DMSA (n = 2; 1 VUR grade III, 1 VUR grade IV)]. At T2, 9 out of 51 children (17.6%) had an increased Alb/Cr ratio [All 9 children had a loss in renal parenchyma: one renal scar (n = 4), more than one renal scar (n = 2), atrophic kidney (n = 3)]. Alb/Cr mean value, for all the children, was significantly higher at T1 [1.63 (2.95) μg/μmol] than at T2 [1.04 (1.28) μg/μmol] (p = 0.006). No relation was found between Alb/Cr values and VUR grade at T1 or T2.

Conclusions: The increase in Alb excretion appears to be mostly a hyperfiltration marker in children with VUR. The measurement of Alb excretion may be useful in the follow up of these children.

PS3-SAT-196

N-acetilglucosaminidase is a marker of high pressure at the urinary tract in vesicoureteral reflux

M. J. Hernández-González* ¹, S. González-Cerrato¹, N. Álvarez-Martín¹, M. Monge¹, M. I. Luis-Yanes¹, L. Antón², V. García-Nieto¹

¹Hospital Nuestra Señora de Candelaria, Pediatric Nephrology Unit, Santa Cruz de Tenerife, Spain, ²Hospital Nuestra Señora de Candelaria, Pediatric Surgery Unit, Santa Cruz de Tenerife, Spain

Introduction: N-acetylglucosaminidase (NAG) is a lysosomal enzyme produced by renal proximal tubular cells and has been widely used as a marker indicator of renal tubular damage. A urinary NAG level increase is related to a higher transference from inside the cells to tubular space because of a proximal tubule disturbance. In vesicoureteral reflux (VUR), two mechanisms may cause renal function impairment, a high pressure at the urinary tract and a loss of renal parenchyma.

Patients and methods: We have measured NAG/creatinine ratio (NAG/Cr) in two first morning urine specimens collected at diagnostic time and after VUR resolution in 27 children (13M, 24F) with VUR.

Results: 10 out of 27 patients (37%) had an increased NAG/Cr ratio at diagnostic time, but after VUR resolution every patient exhibited a normal NAG/creatinine ratio. NAG/Cr values, measured at the time of diagnosis were higher as the intensity increased VUR [2,99 (3,85) U/gr in mild VUR (grade I y II) (n = 5); 7,54 (11,54) U/gr in moderate VUR (grade III) (n = 13); 17,97 (53,9) U/gr in severe VUR (grade IV y V) (n = 9)]. NAG/Cr was normal in 100% of patients with mild VUR (grade 1 and 2). NAG/Cr value at the time of diagnosis was increased in 46% of children with moderate VUR and in 44% of children with severe VUR. We found a statistically significant correlation between NAG/Cr ratio and other renal function parameters as maximum urinary osmolality (r = −0.7; p < 0.001) and albumin/creatinine ratio (r = 0.58; p = 0.005).

Conclusions: NAG urinary excretion is a moderate sensitive marker for the high pressure at urinary tract that happens in moderate and severe vesicoureteral reflux. In all the children, NAG excretion became normal when reflux had disappeared.

PS3-SAT-201

Children with isolated congenital renal anomalies; absence of Six1 gene mutations

L. Artifoni* ¹, S. Negrisolo¹, S. Centi, E. Benetti², G. Ghirardo², M. Della Vella¹, L. Murer¹,²

¹Laboratory of Immunopathology and Molecular Biology of the Kidney, Department of Pediatrics “Salus Pueri”, University of Padua, Italy, ²Pediatric Nephrology, Dialysis and Transplant Unit, Department of Pediatrics “Salus Pueri”, University of Padua, Italy

The mammalian Six transcriptional factors genes family comprises six members (Six1–6). Their products share two highly conserved domains, the Six domain and the homeodomain. The SIX domain (SD) is responsible for protein-protein interaction, while the homeodomain (HD) is essential for protein-DNA binding. Six genes are widely expressed in many tissues in mammalian organogenesis, including developing ear, branchial arch, and kidney. Six1, homologous to the Drosophila sine oculis is a crucial regulator of renal development expressed in the metanephric mesenchyme (MM) before the initiation of ureteric bud (UB) branching morphogenesis. The human SIX1 gene maps to chromosome 14q23.1 and consists of 2 exons coding for a transcription factor of 284 amino acids that belongs to six/sine oculis homeobox family. Mutations in human SIX1 gene cause branchiootorenal (BOR) or branchiootic (BO) syndrome. Six1−/− mice exhibit renal agenesis. To our knowledge, SIX1 gene has never been examined in humans with nonsyndromic congenital anomalies of the kidney and urinary tract (CAKUT). Therefore we investigated whether mutations or deletions of this gene are associated with congenital renal disorders. 30 unrelated children and young adults with CAKUT (hypo/dysplasia with or without associated primary vesicoureteric reflux, renal agenesis) were retrospectively recruited for SIX1 sequence variations analysis. All patients did not have hearing loss or branchial arch defects. SIX1 coding sequence was screened by HRMA and direct sequencing. A quantitative comparative Real-time was performed in order to detect the presence of SIX1 gene deletion. We did not find mutations or deletions in SIX1 coding regions in our population. Our findings suggest that alterations in the SIX1 coding sequence of gene are probably not a major cause of nonsyndromic CAKUT. Further studies are needed, both to increase the number of patients to be tested, both for analyzing non-coding regulatory regions of SIX1 gene.

PS3-SAT-206

Surprising positive effect of desmopressin with nootropics in children with resistant nocturnal enuresis

J. Liška* ¹, V. Holeček¹, Š. Sobotová¹, M. Kepková¹

¹Mulač Hospital, Plzeň, Czech Republic

In the years 2003–2007 62 patients aged from 8 to 17 years, being 42 boys and 20 girls with resistant nocturnal enuresis (NE) were studied. After two years of experiments with desmopressin (Minirin) to resistant NE we were succesful in 68%. The original treatment included desmopressin combined with oxybutinin. In spite of this combination the positive effect reached only 77%. We have observed sleeping disorders. Having had only moderate effect using the above mentioned combination we decided to add piracetam. 20 μg/daily of desmopressin, 0,2 mg/kg of oxybutinin and 30–40 μg of piracetam were administrated at bedtime. The application of this combination continued up to one and a half year. Due to this effect we eliminated after 6 months from this combination oxybutinin, after 9 months of therapy we reduced desmopressin to the half. After one year we eliminated desmopressin at all and after 15 to 18 months we stopped the application of piracetam. Two relapses of NE occured. After the application desmopressin with piracetam after 6 months the therapy was stopped and NE didn’t occur further. In the years 2007–2010 we eliminated the therapy with oxybutinin and to the other 32 patients with resistant NE we increased piracetam therapy by 50%. This resulted to positive and long-term effect in 97% of patients. We didn’t find any side-effects of desmopressin and piracetam in the whole group.

Conclusion: Our limited experience showed surprising good effect of combination desmopressin and piracetam.

PS3-SAT-212

Procalcitonin as a predictor of acute pyelonephritis and risk for renal scarring in children with a first febrile urinary tract infection

J. Putnik* ¹, N. Stajić¹, A. Paripović¹, E. Jakšić², R. Bogdanović³

¹Institute of Mother and Child Healthcare, Department of Nephrology, Belgrade, Serbia, ²Clinical Centre of Serbia, School of Medicine University of Belgrade, Serbia, ³Institute of Mother and Child Healthcare, Department of Nephrology, Belgrade, Serbia. School of Medicine University of Belgrade, Serbia

Objectives: Urinary tract infection (UTI) is a second most common infection in infants and young children. Renal infection may cause parenchimal scarring and requires more aggressive investigation and follow-up monitoring, so the distinction between acute pyelonephritis and UTI without renal involvement is very important. The aim of our prospective study was to investigate the diagnostic value of serum procalcitonin levels in children with first febrile urinary tract infection in prediction of: renal parenchimal involvement; coexistence of vesicoureteral reflux and risk for permanent renal damage.

Materials and methods: Serum C-reactive protein and procalcitonin were measured in 100 children, aged 1–90 months (mean 18 months), admitted for suspected pyelonephritis. Renal parenchimal involvement was assessed by ^99mTc-dimercaptosuccinic acid (DMSA) scintigraphy within 3–7 days after admission. Presence and grading of vesicoureteral reflux was estimated by voiding cystourethrography. Control DMSA performed six months later, demonstrates renal scars formation.

Results: The diagnosis of pyelonephritis was established in seventy seven of 100 patients (77%) according to positive DMSA scan. Among 96 investigated patients 29% had vesicoureteral reflux. On the DMSA scintigraphy obtained after 6 months, twenty nine of 71 patients (41%) had renal scars. The mean PCT level was significantly higher in acute pyelonephritis than in UTI without renal lesions (2, 45 ± 3, 01 ng/ml vs 0,45 ± 0,20 ng/ml, p < 0.001). For the prediction of acute pyelonephritis, the sensitivity and specificity of PCT measurements were 93,5% and 60,9%. No correlation was found between elevated level of procalcitonin and vesicoureteral reflux or renal scarring.

Conclusion: Serum PCT level is an excellent, very specific marker for early diagnosis of acute pyelonephritis, but inadequate for prediction of VUR and renal scarring.

PS3-SAT-214

Mid-aortic syndrome with bilateral arterial stenosis: treatment by aorto-aortic bypass and renal auto-transplantation

M. Djaziri*¹, P. Krug¹, E. Allain-Launay², G. Roussey-Kesler², R. Salomon¹, P. Niaudet¹, C. Chardot³

¹Pediatric Nephrology, Necker-enfants malades Hospital, France, ²Pediatric Nephrology, Nantes Hospital, France, ³Pediatric Surgery, Necker-enfants malades Hospital, France

Fibromuscular dysplasia is frequently responsible for renal artery stenosis and severe hypertension. In some cases an extension of the disease to different territories is observed. We report on a 3 year-old girl, with bilateral renal artery stenosis and mid-aortic syndrome treated by aorto-aortic bypass. Severe arterial hypertension (180/130 mmHg) was discovered fortuitously at the age of 2 years and a half. An angioscan showed multiple artery stenosis including the abdominal aorta next to renal arteries ostia, the renal arteries as well as the superior mesenteric and celiac arteries. Creatininemia was normal, there was no symptoms related to mesenteric ischemia. Supra-aortic cerebral vessels were normal. The medical treatment associating nifedipine, acebutolol, hydrochlorothiazide, minoxidil and prazosine failed to normalized blood pressure. Endoluminal balloon dilatation of the right renal artery had only partial effect on blood pressure. A surgical procedure was then considered. The aortic stenosis was treated with an aorto-aortic graft. Surgical correction of the renal artery artery stenosis consisted in bilateral renal autotransplantation. Blood flow in the aorta was interrupted during 20 minutes during the procedure. Renal arteries were anastomosed on iliac arteries. After the intervention, antihypertensive medications were stopped and renal function recovered immediately. Afterwards, the renal echo-doppler showed a good vascularization of both kidneys. One week later, nifedipine was reintroduced because of moderate HTN. In conclusion, when medication and endoluminal angioplasty failed, mid-aortic syndrome with bilateral renal artey stenosis can be treated with aorto-aortic bypass and bilateral autotransplantation even in small children.

PS3-SAT-216

Blood pressure load and its association with end organ damage with respect to different cut-off levels in ambulatory blood pressure monitorization

M. Torun Bayram*¹, D. Alaygut¹, B. Kasap Demir¹, A. Soylu¹, M. Türkmen¹, S. Kavukçu¹

¹Dokuz Eylul University Medical Faculty Department of Pediatrics, Izmir, Turkey

Introduction: When blood pressure load (BPL) in ambulatory blood pressure monitorization (ABPM) is determined, cut-off level for hypertension (HT) may be used as either 95p of casual or of ABPM measurements. In the present study, we aimed to evaluate the rate of HT and its association with end organ damage (EOD) with respect to both cut-off levels.

Patients and methods: Patients evaluated by ABPM for HT were enrolled. They were evaluated for daytime/nighttime sBPL, dBPL, sHT and dHT with respect to 95p of both casual (Method 1) and ABPM (Method 2). Those with BPL >25% were accepted as hypertensive. The results obtained in both methods were compared. Furthermore, HT defined according to both methods was evaluated for predicting EOD.

Results: There were 201 patients (73 female, mean age 163 ± 43 months). Method 1 detected more daytime sHT (56% vs 42%, p = 0.005), but less nighttime dHT (8% vs 32%, p < 0.001). EOD was detected in 23 of 81 patients evaluated. When rate of EOD was compared in patients with or without HT, only those with daytime dHT had increased EOD in both Method 1 (9/15 vs 14/66, p = 0.003) and Method 2 (7/14 vs 16/67, p = 0.049). When Method 1 and Method 2 were compared for predicting EOD, Method 2 was found to be superior with respect to the presence of nighttime dHT in predicting EOD (3/23 in Method 1, 9/23 in Method 2, p = 0.044, OR 4.3).

Discussion: Daytime sHT is more frequent when casual cut-off level is used, while nighttime dHT is more frequent when ABPM cut-off level is used. EOD risk is increased in those with daytime dHT in both methods. Using ABPM cut-off level for the definition of nighttime dHT increases the number of patients with the diagnosis of HT 4-fold, while predictive value for detecting patients with EOD increase as well.

PS3-SAT-223

Kidney function and blood supply in children with inherited thrombophilia

O. Chugunova¹, M. Shumikhina* ¹

¹Russian State Medical University, Moscow, Russian Federation

The purpose of the study was to determine kidney function and blood supply in children with inherited thrombophilia. Methods: Laboratory investigation was performed in 35 children with identified inherited thrombophilia, 15 of them have arterial or venous thrombosis, 20—asymptomatic with strong family history of thromboembolism (24 boys, 11 girls, the mean age 6,8 ± 3,3 years). Most frequently causes of inherited thrombophilia were homozygous mutation in methylenetetrahydrofolate reductase gene (37,1%) with hyperhomocysteinemia upper 12 μmol/l, Leiden mutation (20%) decrease of antithrombin (14,3%), protein C (8,6%) and S (5,7%) levels activity. The laboratory investigations enclose the microalbuminuria test in sample of morning urine specimens, serum creatinine and lipoprotein (a). The ultrasound examination with Doppler test was also performed. Results: All of the patients have no reduction of kidney function. The mean glomerular filtration rate (by Schwartz formula) was 95,0 ± 3,6 ml per minute. The microalbuminuria was present in 9 patients (25,7%). In 5 children with inherited thrombophilia and increased blood level of lipoprotein (a) in 2–4 times (up to 175 mg/dl) renal infarction was detected using ultrasound examination. This condition was asymptomatic because of its small size and the sonographic sign was hyperechogenic avascular wedge shape zone. In consort with hematologist all these children were prescribed the anticoagulant therapy. During the follow up period (from 3 to 24 months) new zone of the infarction has not appeared. Conclusion: all patients with inherited thrombophilia and increased levels of lipoprotein (a) in 2 times and more must undergo the US examination because of the possible presence of zones of kidney infarction.

PS3-SAT-227

Two boys with obstructive lesions of both the aorta and urethra

D. Noone*¹, S.D. Marks¹

¹Department of Paediatric Nephrology, Great Ormond Street Hospital for Children, London, UK

Introduction: The aetiopathogenesis of posterior urethral valves (PUV) remains unclear although may result from a combination of genetic and environmental factors. The same is true of left ventricular outflow tract obstruction including coarctation but there is a strong genetic component recognised.

Methods and results:

Case 1: The first boy had an antenatal diagnosis of bilateral hydronephrosis with postnatal confirmation of VUR and PUV, which were resected. At 2 ½ years of age he was noted to be hypertensive with a systolic blood pressure (BP) above the 95th centile for age. This coincided with having his BP measured on his upper limb rather than his lower limbs. An echocardiogram found turbulent flow with diastolic tail in the abdominal aorta suggestive of an abdominal coarctation confirmed on MRA with DSA showing severe irregular supracoeliac stenosis from about T10 to T12. He had the stenosis angioplastied and stented but needed repeat angioplasty and dilatation of the stent at age five and six years.

Case 2: The second boy was born at term and had normal antenatal scans. He presented at four weeks of age with urosepsis and a history of poor urinary stream and failure to thrive and subsequently was diagnosed with PUV. A murmur prompted an echocardiogram that showed a discrete coarctation distal to the left subclavian artery. His coarctation was repaired at 6 weeks of age and his valves ablated three weeks later. He required a balloon dilatation of a recoarctation at seventeen months, at four and thirteen years.

Conclusions: We report for the first time aortic coarctation in association with PUV. We are looking for other cases to perform linkage analysis or genome wide microarrays as possible candidates may include genes encoding transcriptional factors critical for both cardiac and renal tract morphogenesis and development, such as in the NOTCH pathway or T-box factors.

PS3-SAT-230

Revascular hypertension—a 20 year -single center experience

S. Collopy*¹, A.C. Hebbialobo¹, L. Susuki¹, J.C. Marino¹, E.A. Furusawa¹, V.H. Koch¹

¹Instituto da Criança—clinics hospital—Medicine school of university of São Paulo, Brasil

Objectives: Describe the etiology, clinical features, diagnostic methods, treatment and follow up of children with RVH.

Methods: Retrospective descriptive study wich evaluated 18 children with RVH from january 1990 to march 2010.results:initial age varied from 8 to 172 months; 55,5% were male; the following up median time were 24,5 months. As initial presentation, 44% were asymptomatic.hypertensive encephalopathy,abdominal pain, cardiac insuffiency and cerebral vascular accident were other features. 94% had severe high blood pressure (BP) while 55% were using 3 or more drugs and 77% had, at least, one target-organ injury. 78% of pacients were diagnosed with RVH by doppler scan ultrasound as screening exam, although all pacients were submitted to a invasive imaging exam (angiography, angio CT or angio MRI)to confirm diagnosis.In 50% of the cases, the doppler ultrasound identified the same number of injured arteries as the invasive imaging exams.61% of patients had bilateral renal vascular lesions and 73% of those had up to 2 extra-renal lesions. RVH were due to: takayasu’s arteritis (6), fibromuscular dysplasia (5), neurofibromatosis (2), renal artery aneurysm (1), renal artery extrinsic compression (1), arterial trombosis (1), willians syndrome (1), medium aorta syndrome (1). Treatment consisted in angioplasty (6), revascularization surgery (6) and conservative (6). 66,6% of children had their BP controlled by the end of follow up, whereas 33,3% without the use of any drugs. initial ecocardiographic alterations were normalized in 90% of patients and 77% improved their glomerular filtration rate. CONCLUSIONS: most of target-organ lesions were reversible by BP control. the doppler scan ultrasound should be considered as a good screening exam for renal vascular lesions. our case series might differ from the literature as far as etiology goes, for we are a reference center for rheumatologic diseases.

PS3-SAT-231

Subclinical cardiovascular abnormalities in patients with juvenile systemic lupus erythematosus

N. Canpolat*¹, O. Kasapcopur², S. Caliskan¹, S. Gokalp³, M. Bor⁴, M. Tasdemir¹, L. Sever¹, N. Arisoy²

¹Department of Pediatric Nephrology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey, ²Department of Pediatric Rheumatology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey, ³Department of Pediatric Cardiology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey, ⁴Department of Pediatrics, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey

Objectives: To evaluate subclinical cardiovascular abnormalities in children and adolescent with systemic lupus erythematosus (SLE).

Methods: Non-invasive cardiovascular assessments were made on 22 patients with juvenile SLE (20 girls, aged 15.0 ± 2.7 years) with GFR ≥90 ml/min/1.73 m². Ambulatory blood pressure monitoring (ABPM) was used for the definition of hypertension. Ultrasonographic examinations of the heart and carotid artery were performed to evaluate left ventricular hypertrophy (LVH), carotid intima-media thickness (IMT) and carotid artery distensibility. Aortic (carotid-femoral) pulse wave velocity (PWV) and pulse wave analysis (PWA) were performed for the assessment of arterial stiffness. To compare the PWV and PWA of the patients, two control groups were formed; matched for age/sex (control A; n = 22) and for height/sex (control H; n = 22).

Results: The median disease duration was 39.5 (iqr 26.0–65.2) months. Twelve patients had active disease characterized by SLEDAI ≥3 and none of the patients had organ damage as identified by SLICC. The mean left ventricular mass (LVM) index was 37.5 ± 11.2 g/m2.7 and 6 patients (27%) had LVH. Carotid IMT-SDS was 2.03 ± 1.68; twelve patients (54%) showed increased carotid IMT. Patients had higher aortic PWV (5.32 ± 0.87 m/s) compared to both control groups (4.98 ± 0.45 m/s for control A, and 4.84 ± 0.38 m/s for control H); however the difference was significant only for control H (p = 0.041). Aortic PWV was found to be correlated with average index SBP on ABPM (r = 0.74, p < 0.001) and BMI-SDS (r = 0.41, p = 0.036). No correlation was found between PWV and laboratory parameters including s-CRP, ESR, C3, C4, anti-ds DNA, ACP IgM or ACP IgG levels. PWV showed a significant association with carotid distensibility calculated from carotid end-diastolic and peak systolic internal dimensions from the M-mode images of carotid artery (r = −0.57, p = 0.007). Aortic augmented pressure and augmentation index (AI) using PWA were similar in patients and controls.

Conclusion: Juvenile SLE patients without organ damage (SLICC = 0) have an increased subclinical cardiovascular abnormalities.

PS3-SAT-232

Spectrum of hepatocyte nuclear factor 1beta mutations in a prospective cohort of patients with congenital renal abnormalities

D. Mekahli*¹, T. Van Ackere¹, A. Corveleyn², M. Van Dyck¹, E. Van Hoyweghen¹, N. Knops¹, R. Lombaerts-Van Damme¹, K. Devriendt², E. Levtchenko¹

¹Department of Pediatric Nephrology, University Hospital Gasthuisberg, Leuven, Belgium, ²Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium

Background: Hepatocyte nuclear factor 1 beta(HNF1β) is a transcription factor with a crucial role in the gene expression in various tissues. Renal and extra-renal phenotype in these patients is variable, and selection criteria for genetic testing are not well evaluated. We defined screening criteria for HNF1β analysis and tested them in a prospective cohort of patients with congenital abnormalities of kidneys and urinary tract(CAKUT).

Methods: Between 01/01/2009 and 31/12/2010, 67 children with CAKUT were prospectively evaluated based on the presence of at least one major criterium (fetal bilateral hyperechogenic kidneys, cystic kidneys of unknown aetiology(CKUA), multicystic dysplastic kidney(MCDK), renal agenesis(RA), hypoplastic/dysplastic kidneys(HDK)) or at least 1 minor criterium (vesico-ureteric reflux, renal ectopia, hydronephrosis) combined with one or more extra-renal criteria (diabetes mellitus (DM), gout/hyperuricaemia, hypomagnesemia, hypokalemia, cholestasis).

Results: Median age was 2.0 (0.0–16.4) years, 42 males. Renal phenotypes at diagnosis were HDK (n = 24), RA (n = 13), MCDK (n = 28) and CKUA (n = 2). Ten children (15%) were HNF1β positive (4 heterozygous deletion of the entire gene, 2 nonsense and 2 missense point mutations, 2 splice site mutations) from whom 2 RA, 7 MCDK, 1 CKUA. Positive family history was in 8 (6 renal disease, 7 DM). Chronic kidney disease (stage ≥2) was found in 8/10 patients. None of them had DM, hypokalemia or hypomagnesemia.

Conclusions: In this prospectively collected series based on well defined criteria, HNF1β mutations were found in 15% of the patients having at least one major CAKUT abnormality. No DM, hypokaliemia or hypomagnesemia could be detected in these patients. However, positive family history of renal disease/DM/gout was present in 8/10 patients compared to 30/57 patients without HNF1β mutations.

PS3-SAT-236

Intravesical hyaluronic acid treatment improves bacterial cystitis and reduces cystitis-induced hypercontractility in rats

N. Yildiz*¹, H. Tugtepe², Z.N. Ozdemir³, D. Akakin⁴, A. Ilki⁵, G. Sener⁶, B.C. Yegen³, H. Alpay¹

¹Marmara University Faculty of Medicine, Department of Pediatric Nephrology, Istanbul, Turkey, ²Marmara University Faculty of Medicine, Department of Pediatric Surgery, Istanbul, Turkey, ³Marmara University Faculty of Medicine, Department of Physiology, Istanbul, Turkey, ⁴Marmara University Faculty of Medicine, Department of Histology-Embriology, Istanbul, Turkey, ⁵Marmara University Faculty of Medicine, Department of Microbiology, Istanbul, Turkey, ⁶Marmara University Faculty of Pharmacy, Department of Pharmacology, Istanbul, Turkey

In order to assess the effect of hyaluronic acid (HA) on E. Coli-induced cystitis, Wistar albino rats(n = 24) were induced with bacterial cystitis by intravesical E. coli(0.5 ml, 2 × 108 colonies/ml) and 3 days after the inoculation, rats were either non-treated, treated with gentamycin(4 mg/kg, 5 days,im) or intravesically HA(0.5 ml, 0.5%). Control group was instilled with saline. On the 8th day of inoculation, bladder samples were taken for histological and functional studies. In detrusor muscle strips, carbachol(10-4-10-8M) contraction responses were calculated as the percentage of 80 mM KCl contraction responses, while relaxation responses to isoprotrenol(10-4-10-10M) and papaverine(100 μM) were calculated. E. coli-induced cystitis in all rats resulted in increased contraction responses to CCh at low concentrations compared to controls(p < 0.01). In rats with cystitis, treatment with HA, but not gentamycin, significantly(p < 0.05) depressed hypercontractility at maximum CCh concentrations. In all rats with cystitis, papaverine-induced relaxation was increased as compared to controls(p < 0.01) and no difference was observed among the cystitis groups. On the other hand, isoproterenol-induced relaxation curves were not different between the studied groups. Histological analysis demonstrated loss of epithelium and inflammatory cell infiltration in the lamina propria of the bladders of untreated cystitis group. In HA-treated group, healing of the uroepithelium was observed, while decreased inflammatory cell infiltration was obvious in the genta-treated group. In conclusion, the results indicate that bacterial cystitis, causing the epithelial inflammation,increased detrusor contractile and relaxant responses. Antibacterial treatment with gentamycin being effective in ameliorating inflammation, had no impact on the contractile dysfunction of the injured bladder. However, HA, in addition to its supportive role in the healing of the epithelium, lowered the increased threshold for contraction. Thus, the results indicate a potential role for HA in the treatment of bacterial cystitis in combination with antibacterial therapy.

PS3-SAT-240

BNP monitoring in an infant with severe hypertension and heart failure

I. Zaluska-Lesniewska*¹, P. Czarniak¹, A. Zurowska¹

¹Department Paediatric Nephrology, Medical University, Gdansk Poland

The diagnosis and management of infant hypertension remains challenging. Severe hypertension can manifest with life threatening symptoms of cardiac failure. In adults natriuretic peptides (NP) are used as markers of cardiovascular diseases and their utility in children is under discussion. The peptides BNP and NTpBNP are released from the heart in response to pressure and volume overload and might be useful in the diagnosis and management of severe hypertension in infants.

We report a 4 month old infant with stage 2 hypertension with heart failure. The child was admitted to an ICU due to cardiac shock. Following resuscitation and resolution of clinical symptoms of heart failure the girl was referred for further evaluation of severe hypertension. She demonstrated massive proteinuria with normal renal function, high renin activity (2300 uIU/ml) and elevated BNP (13000 pg/ml). Echocardiography showed severe left ventricular hypertrophy (LVH) with normal ejection fraction. Initial intravenous labetalol treatment followed by multi drug antihypertensive therapy lowered the blood pressure to values between 95–99th centile. In spite of the lack of clinical symptoms of heart failure her BNP levels continued to be high (3000 pg/ml). The values normalized (BNP <10 pg/ml) following further decrease in blood pressure <95 centile and subsequent improvement in LVH on seven antihypertensive drugs. CT angiography revealed critical stenosis of the left renal artery and an afunctional left kidney. A nephrectomy was performed and to date the child is normotensive on single drug therapy (ACE) with complete resolution of LVH and normal BNP levels.

Conclusions:

• 1. BNP may serve as sensitive laboratory marker of LV dysfunction in infants with severe hypertension in the absence of classical symptoms of heart failure.

• 2. BNP measurements can aid the management of severe hypertension in infants as a laboratory marker of pressure and volume overload.

PS3-SAT-251

Early renal abnormalities in children with autosomal dominant polycystic kidney disease

L. Selistre*^2,3,4, M.B. DeGeorges¹, V.C. de Souza^1,2,5, B. Ranchin¹, S. Lemoine², A. Hadj-Aissa², P. Cochat^1,2,5,6, L. Dubourg^1,2,5,6

¹Département de Néphrologie Pédiatrique, Hospices Civils de Lyon, Lyon, France, ²Exploration Fonctionelle Rénale et Métabolique, Hospices Civils de Lyon, Lyon, France, ³Pontificia Universidade Católica do Rio Grande do Sul, Rio Grande do Sul, Brazil, ⁴Universidade de Caxias do Sul, Caxias do Sul, Brazil, ⁵Université Claude Bernard Lyon, Lyon, France, ⁶FRE 3310, CNRS, Lyon, France

Objective: The aim of our study was to characterize early renal abnormalities in children with ADPKD.

Methods: Renal function was assessed in 52 prevalent ADPKD children (Ravine criteria) (54% boys, mean age = 10 ± 4.2 [1–17] years). Systolic (SBP) and diastolic (DBP) blood pressure were measured and expressed as percentile for height and age (WHO charts 2007). Glomerular filtration rate was measured by inulin clearance (iGFR, ml/min per 1.73 m²) and urinary albumine: creatinine ratio (Ualb/cr, mg/mmol) was obtained concomitantly. Tubular assessment was performed by measuring Na, Cl and K reabsorption rate (RR) , TmP/GFR, fractional excretion of uric acid (FEUA) and urinary magnesium and calcium: creatinine ratio (UMg/cr, Uca/cr).

Results: Mean and Median SBP and DBP percentiles were 55 ± 28 and 59 [1–100], 50 ± 29 and 54 [4–100], respectively with 3 patients having a SBP and DBP above the 95th percentile and 1 child treated by an angiotensin-converting enzyme inhibitor. The mean ± SD iGFR was 115 ± 26 [47–168] but 5 children had an iGFR <90 and 11 showed hyperfiltration (GFR > 135). 24/51 patients had microalbuminuria (2 < Ualb/cr < 20) and 5 macroalbuminuria (>20). Electrolytes RR, TmP/GFR, UMg/cr, UCa/cr were within normal ranges in all patients but FEUA was increased (>12%) in 12 patients without decreased plasma UA concentration, suggesting minimal tubular abnormalities. CONCLUSION: ADPKD children may present with early renal dysfunction including arterial hypertension in 6%, albuminuria in 57% and decreased GFR in 11%. Slight tubular abnormalities have been observed in 23% of patients and could be early symptoms of tubular dysfunction. In conclusion, renal function in children with ADPKD should be regularly assessed in order to manage early renal dysfunction, and even consider further therapeutic intervention.

PS3-SAT-254

Postnatal assessment of the infants with antenally detected renal pelvic dilation

S. Emre¹, I. Bilge¹, Z. Yuruk*¹, A. Yilmaz¹, H. Ander², B. Aksu¹, A. Sirin¹

¹Istanbul University Istanbul Medical Faculty, Pediatric Nephrology Department, Istanbul, Turkey, ²Istanbul University Istanbul Medical Faculty, Urology Department, Istanbul, Turkey

Widespread application of antenatal ultrasound (USG) lead to early detection of congenital abnormalities of the urinary tract. Approximately half of these abnormalities consists of renal pelvic dilation (RPD). The aim of this retrospective study was to evaluate the results of postnatal diagnosis and follow up of the infants with RPD.

Two hundred and eighty infants with the diagnosis of antenatal RPD were enrolled in this retrospective study. Mild dilation was defined as pelvic diameter (pd) <15 mm, moderate dilation as pd:15–20 mm, severe dilation as pd >20 mm

Of the 280 patients, 70 (25%) were female and 210 (75%) were male. Mean follow up duration was 16.3 ± 18.6 months (6–127). RPD was not sustained in 26 infants (9.35%) in postnatal USG performed at the seventh day of life. RPD was unilateral in 158 (56.4%) and bilateral in 96 (34.3%). Of the 350 renal units with RPD in postnatal USG, 197 (56.3%) were mild, 84 (24%) were moderate and 69 (19.7%) were severe.

Among the infants with mild dilation, 95 (70.4%) were non-obstructive pelvic dilation, 14 (10.4%) were vesicoureteral reflux (VUR), 12 (8.9%) were ureteropelvic junction obstruction (UPJO), 3 (2.2%) were ureterovesical junction obstruction (UVJO), 1 (0.7%) was posterior ureteral valv (PUV). In moderate dilation group, 29 (44.7%) were non-obstructive pelvic dilation, 15 (23%) VUR, 12 (18.5%) were UPJO, 1 (1.5%) were UVJO, 3 (4.7%) were PUV. In severe dilation group, 10 (13.2%) were non-obstructive pelvic dilation, 5 (9.6%) VUR, 18 (34.6%) were UPJO, 1 (1.9%) were UVJO, 5 (9.6%) were PUV.

RPD disappeared in 34.9% of renal units with mild dilation on follow up and pd decreased in 26.4%, was increased in 9% and remained stable in 29.7%. The rate of spontaneous resolution of VUR was 34%. Renal function deteriorated in 1 patient with PUV.

In conclusion, majority of mild or moderate antenatal RPD is due to non-obstructive pelvic dilation and VUR. Antenatal USG is a sensitive method to detect urinary tract abnormalities with only 10% false positive results.

PS3-SAT-255

Renal involvement in HSP paediatric patients

S. Abdulsamea*¹, T. Rajkowski¹, M. Eisenhut¹,

¹Luton and Dunstable Hospital NHS foundation trust, London, UK

In this retrospective analysis, we reviewed 26 paediatric patients presented with HSP to our hospital. The main concern was to address the extense of renal involvement and hypertension in this group of population. The mean age was 6.7 +/− 2.4 years (range 2–10 years), 15 (57%) were males. In 83% there was proceeding Upper respriatory tract infection, and in 10% no clear history was found. In 3 cases HSP was recurrent.

Hypertension was found in 48% of our group of patients at time of presentation, which was managed conservatively with close monitoring of BP reading. Haematuria was found in 10 cases (38%) at time of presentation, which was ranging between two to three plus of blood tested by urine dipstick. Protinuria was present in 15 cases (57%) with alb/creat ratio ranging between 1.1 to 330. Long term follow up of these cases showed no more hematuria or protinuria. High creatinine was present in 2 cases at presentation, that improved on follow up analysis. Long term follow up ranged between 6 weeks to 2 years. There were no more haematuria or protinuria in all of our cases. Skin rash was present in all of our cases, which was atypical in 5 cases. Joint involvment; in the form of arthritis/arthralgia; was present in 16 (61%) cases. in average 1–4 joints were involved. Management was in the form of analgesics, and all cases had thier joints resolved. Abdmonial vasculitis was present in the form of abdominal pain in 16 cases (61%). In one case there was complicated intususception which was managed surgically.

In conclusion, hypertension and renal involvement is an often, but not long lasting finding in HSP paediatric patients.

PS3-SAT-256

Attention deficit/hyperactivity disorder (ADHD) is a frequent comorbidity among children suspected of hypertension

S. Grisaru*¹, J. Mah², L. Hamiwka¹

¹Department of Pediatrics, University of Calgary, Calgary, Canada, ²University of Calgary, Calgary, Canada

Childhood hypertension has recently been shown to be associated with behavioral abnormalities and attention deficit/hyperactivity disorder (ADHD). Pharmacotherapy for ADHD has long been known to cause a modest elevation in blood pressure (BP) and heart rate. Our objective was to evaluate the burden of ADHD among patients referred to the nephrology clinic for evaluation of suspected hypertension.

Our tertiary care pediatric referral center serves a population of roughly 1.5 million inhabitants. All children older than 6 years of age referred for evaluation of suspected hypertension are screened with an ambulatory blood pressure monitoring test (ABPM) before their first visit in the nephrology clinic. We reviewed the electronic database of ABPM tests performed from 2005 to 2010. The Welch Allyn ABPM 6100® monitor was used with parameters according to reference values provided by Whül et al. Tests were considered abnormal if the average blood pressure was higher than the 95th percentile or the systolic/diastolic loads were higher than 25%.

A total of 1158 ABPM tests were performed in 580 children. After excluding follow-up and routine tests for patients with known hypertension, acute or chronic renal disease and kidney transplant recipients; 229 ABPM test were left which were performed in children referred for suspected hypertension. Forty eight children (21%, 40 males) from this group had a history of ADHD. Their average body mass index Z-score was 0.16 (SD 1.6) and most of them were treated with one of the pharmacotherapeutic agents indicated for ADHD. Screening ABPM test in these children was abnormal in 23 (48%) while among children without ADHD only 24% (44/181) of the ABPM tests were abnormal (p < 0.05).

These preliminary data suggest that children with ADHD may represent a population suitable for early intervention after screening for hypertension with ABPM, however prospective studies are required to further establish this hypothesis.

PS3-SAT-263

S100 calgranulins in urinary tract infection

A. Yilmaz*¹, A. Gedikbasi², A. Kiyak³, M. Mulazimoglu⁴, G. Aydogan³, T. Ozpacaci⁴, S. Hatipoglu²

¹Istanbul University Istanbul Medical Faculty, Pediatric Nephrology Department, Istanbul, Turkey,²Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey, ³Bakirkoy Maternity and Childrens Hospital, Istanbul, Turkey, ⁴Okmeydani Training and Research Hospital, Istanbul, Turkey

The calgranulins are a subgroup of S-100 calcium-binding protein family that is expressed in renal epithelial cells and neutrophils. The calgranulins have protective anti-infective and anti-inflammatory effects. The aim of our study was to assess whether urine levels of calgranulins increase in children with UTI and to determine the optimal cut-off level for urine calgranulins to predict UTI in children.

Seventy-four patients with UTI (57 female, 17 male; mean age: 7.31 ± 4.13 years), 40 children with bacterial contamination in their urine culture (19 female, 21 male; mean age: 2.72 ± 3.67 years) and 51 healthy children (21 female, 30 male; mean age: 6.69 ± 3.8 years) were enrolled the study. Urine samples were obtained by catheter from patients who presented with symptoms suggesting UTI. UTI was diagnosed if there was significant bacteriuria (≥10.000 cfu/ml) in the urine culture. Urine samples for culture were obtained by collecting bag or midstream urine from asymptomatic patients who have been followed up for recurrent UTI in our outpatient clinic and the control group. The children in the control group were excluded from the study if they had bacterial growth in their urine, whereas second urine sample was obtained by catheter from asymptomatic patients. If there was no bacterial growth in the second urine culture by catheter, the patient was enrolled in the contamination group.

Random urine samples were obtained for measurement of calgranulins and creatinine from both the control and contamination groups; whereas collection of urine samples were done prior to treatment of UTI at the time of presentation (pt) and after treatment (at). Urine levels of S100A9 (Calgranulin B) and S100A12 (Calgranulin C) were measured by ELISA.

Urine S100A9 levels prior to treatment (uS100A9pt) were significantly higher in the UTI group than in the contamination and the control groups (128.25 ng/ml, 17.11 ng/ml and 18.49 ng/ml, respectively; p = 0.0001). Using a cut-off 65.74 ng/ml for uS100A9pt for prediction of UTI, sensitivity and specificity were 92% and 98%, respectively (AUC: 0,97). Urine S100A9pt levels were not different in the patients with and without pyelonephritis (p > 0.05). There was no significant relationship between uS100A9pt and presence of renal scar or vesicoureteral reflux (p > 0.05). Mean urine S100A9 level after treatment (uS100A9at) decreased to 18.34 ng/ml in UTI group (p = 0 .0001). Urine S100A12 levels prior to treatment (uS100A12pt) were significantly higher in the UTI group than in the contamination and the control groups (370.58 ng/ml, 29.04 ng/ml and 23.77 ng/ml, respectively; p = 0.0001). Using a cut-off 99.79 ng/ml for uS100A12pt for prediction of UTI, sensitivity and specificity were 98.6% and 99%, respectively (AUC: 0,99). Urine S100A12pt levels were not different in the patients with and without pyelonephritis (p > 0.05). There was no significant relationship between uS100A12pt and presence of renal scar or vesicoureteral reflux (p > 0.05). Mean urine S100A12 level after treatment (uS100A12at) decreased to 50.26 ng/ml in UTI group (p = 0.0001).

Our findings show that both urine S100A9 and S100A12 levels increase in children with UTI and they can be used as indicators for prediction of UTI in children with high sensitivity, specificity. Further investigations with larger patient groups are required to confirm our results.

PS3-SAT-280

Superiority of desmopressin as oral lyophilisate formulation compared to tablet, related to less interference by associated foodintake

A. De Guchtenaere¹, A. Raes¹, J. Dehoorne¹, E. Van Laecke¹, P. Hoebeke1, C. Van Herzeele¹, J. Vande Walle* ¹

¹University Hospital Ghent, Ghent, Belgium

Introduction: Desmopressin is a first-line treatment in MNE(Monosymptomatic Nocturnal Enuresis). The tablet 200 μg and MELT (oral lyophilisate) 120 μg are considered bioequivalent based on pharmacodynamic tests during oral water-load. In this study we compared pharmacodynamic data of desmopressin tablet and lyophilisate formulation, in addition to a standardized meal. This design allows extrapolation to clinical reality, where the time-interval for school-aged children between evening-meal and medication intake (one hour before bedtime) is limited. We hypothesize 1) a faster PD response and 2) a higher concentrating and 3) anti-diuretic activity for desmopressin MELT formulation compared to the tablet with simultaneous food-intake.

Material and methods: 19 children (4F/15M) with MNE, partially responding to desmopressin tablet treatment were recruited in a tertiary centre, mean age 12.1 y. Two tests were performed on separate days under identical, standardized conditions, starting with a 15 ml/kg waterload. After achieving maximal diluting capacity, standardized meal was administered, followed by desmopressin tablet (T-test) or desmopressin lyophilisate /MELT (M-test) administration. Diuresis-rate was measured hourly, as well as urinary osmolality on every sample.

Results: All patients achieved maximal diluting capacity after oral water-load. In the early response phase more than 25% of patients have a higher diuresis-rate with tablet compared to MELT and reached statistical significance in the plateau phase (U3–U5) and the duration of action (U5–U8) (p < 0.02 and p < 0.005 respectively) . For desmopressin MELT, overall smaller standard deviations in diuresis-rate are remarkable. Similarly, concentrating capacity demonstrated no significant differences in the early response- phase, in contrast with significant differences in the plateau phase and the duration of action (p < 0.036 and p < 0.001 respectively).

Conclusions: In combination with a meal, desmopressin MELT formulation has a superior pharmacodynamic profile in comparison with the tablet, making it more suitable for the younger age group where time- interval between meal and drug administration is limited.

PS3-SAT-281

Pharmacokinetic characteristics of desmopressin oral lyophilisate (MELT) and tablet formulation in children

A. De Guchtenaere* ¹, C. Van Herzeele¹, P. De Bruyne¹, J. Dehoorne¹, A. Raes¹, J. Vande Walle¹

¹University Hospital Ghent, Ghent, Belgium

Objectives: Desmopressin 120 μg oral lyophilisate and 200 μg tablet are considered bioequivalent, based on extrapolation of stdies in a limited number of healthy volunteers, and one dose finding study with the melt in children. However, no comparative pharmacokinetic studies have been execute, confirming this statement.. No data are available on the influence of food-intake on bio-availability of desmopressin tablet or MELT in a pediatric setting, although studies in adults documented that food-intake resulted in significant lower desmopressin plasma-concentration. In this study, we analyzed PK-plasma concentrations of desmopressin tablet and MELT with concomitant food-intake, hypothesizing that mean differences and/or variability in PK-plasma concentrations could only be due to different localizations of mucosal absorption (buccal in MELT, gastro-intestinal with tablet), since only the latter will be influenced by food-intake.

Material and methods: 23 children with MNE (4F/19M), mean age 12.7 y were recruited. Two tests were performed on separate days under identical, standardized conditions with a standardized meal and fluid-intake. The drug wa administered as desmopressin tablet (T-test) or desmopressin lyophilisate /MELT (M-test) was administered immediately after the meal. Desmopressin plasma concentration was measured at hour +1, hour +2 and hour +6 (C1-C2-C6 respectively).

Results: No significant difference in plasma-concentration of the lower dosage 120 μg desmopressin MELT, in comparison with 200 μg tablet, establishing the proposed bioequivalence, even with concomitant food-intake. A significant difference in variability was found, with desmopressin MELT having significantly smaller variance at all C1-C2-C6 (p 0.013, p = 0.037 and p = 0.008 respectively).

Conclusions: This study demonstrates that desmopressin MELT has comparable plasma levels, despite the lower dose, but with a significantly smaller variance, making dosage more predictable in comparison with the tablet. Therefore desmopressin MELT seems more suitable, especially in the younger age group where time- interval in the night between meal and drug administration is limited.

PS3-SAT-292

Impact of urine collecting method on the assessment of bacteriuria in children

J. Arambašić¹, A. Cvitković-Roić* ², I. Berecki¹, N.Turjak¹

¹Clinical Hospital Center Osijek, Croatia, ²Helena Polyclinic Zagreb, Croatia

Objectives and study: To determine reliability of urine cultures in last-stream collector samples and bag samples in comparison with the gold standard- transurethral catheterization.

Methods: Prospective study was done in 75 children (2 to 30 months old). Three urine samples for microbiological analysis were obtained for each child- by urine bag, last-stream collector and by catheterization.

Results: Boys and girls were equally frequent; mean age was 9.4 months. Significant difference was found in urine cultures findings between urine bag samples and samples obtained by catheterization (p < 0.001). The sensitivity of urine bag was 82.3%, specificity 41.4%, positive predictive value 29.2% and negative predictive value 88.9%. There was no statistically significant difference between the last stream collector samples and the samples obtained by catheterization if 105 CFU/mL (p = 1) was considered as a borderline between negative and positive results, while there was marginally significant difference if 104 CFU/mL was considered as a borderline (p = 0.021). By significant bacteriuria of ≥105 CFU/ml the sensitivity was 62.5%, specificity 86.4%, positive predictive value 55.5% and negative predictive value 89.5%; by significant bacteriuria of ≥104 CFU/mL collector samples sensitivity was 94%, specificity 84.5%, positive predictive value 64% and negative predictive value was 98%.

Conclusion: Urine bag is reliable only in a case of a negative urine culture finding. Comparing the culture findings between the collector samples and the samples obtained by catheterization, no statistical difference was found, whereas the findings between the bag-collector samples and the samples obtained by catheterization differed significantly. The last stream collector was more reliable if ≥105 CFU/ml was considered as a borderline between negative and positive results.

PS3-SAT-296

Renal outcome in children with an antenatal diagnosis of severe congenital abnormalities of the kidney and the urinary tract (CAKUT)

J. Hogan* ¹, M. E. Dourthe¹, E. Tudorache^1,3, J. M. Jouannic^2,3, A. L. Sellier-Leclerc¹, T. Ulinski^1,3

¹Pediatric Nephrology, Armand Trousseau Hospital, APHP, Paris, France, ²Obstetrics and Gynecology, Armand Trousseau Hospital, APHP, Paris, France, ³Université Pierre et Marie Curie, Paris, France

Congenital abnormalities of the kidney and the urinary tract (CAKUT) are among the most frequent causes of antenatal consultation. In this retrospective study we evaluate the outcome of children for whom antenatal consultation were performed between 2006 and 2011 in one single pediatric nephrology center and in particular the outcome of children for whom parents declined therapeutic abortion. Then we attempt to evaluate possible predictive factors of renal prognosis. Thirty-three cases of isolated CAKUT were found, 14 therapeutic abortions were proposed and eight of them were refused. Among those eight, three died in the first month of life. The median creatinine level at three days of life was 56 (range 25–316) μmol/L. For the five surviving patients, the median age at the time of analysis was 29 months. All of them had a normal renal function, three without proteinuria and two with a proteinuria of 182 and 235 mg/mmol of creatininuria, respectively. Oligohydramnios was found in the three patients who died. However, two of the five surviving patients also had oligohydramnios. Foetal beta-2 microglobulin blood level was measured in one patient and was increased (9 mg/l). At the age of 29 months this patient has a normal serum creatinine level and a significant proteinuria.

Conclusion: In eight patients for whom therapeutic abortion was proposed for severe CAKUT and refused, five have normal renal function at a median age of 27 months. This demonstrates the difficulty to evaluate renal function outcome in such patients. No predictive factors seem to have enough specificity by itself to motivate a therapeutic abortion proposal, even the presence of oligohydramnios, suggesting the need of long-term follow-up studies.

PS3-SAT-304

Influence of blood pressure on left ventricular hypertrophy (LVH) in children with chronic kidney disease (CKD)

D.Drozdz*¹, J.A.Pietrzyk¹, P.Kwinta², Z.Kordon³, K.Drozdz¹, M. Miklaszewska¹, M. Zachwieja⁴

¹Dialysis Unit, JUMC, Krakow, Poland, ²Dept. of Pediatrics, JUMC, Krakow, poland, ³Dept. of Pediatric Cardiology, JUMC, Krakow, Poland, ⁴Dept. of Nephrology, JUMC, Krakow, Poland

LVH is a predictor of cardiovascular morbidity and mortality in children with CKD. The aim of the study was to assess the influence of BP upon LVH in these patients.

Patients and methods: Study covered 71 children (44 M, 27 F) with CKD stage 1–5 at mean age 11 yrs (SD = 5), height 136 cm (SD = 28) and eGFR 32 ml/min/1.73 m² (SD = 27). Serum creatinine and serum cystatin C levels were evaluated, triple office BP measurement were followed by 24 hrs ABPM. MAP, SBP and DBP were analyzed. LV dimensions and LVMI were evaluated echocardiographicaly with HP 5500 device. Patients were divided into 4 groups according to CKD stage 1–2; 3; 4; 5.

Results: 34 patients showed LVH (3—CKD stage 1–2; 7—stage 3; 10—stage 4; 14—stage 5). In children with LVH significantly higher SBP (118.8 vs. 108.8; p = 0.0016), DBP (72.6 vs. 65.4; p = 0.0093), MAP (88.8 vs. 81; p = 0.004), SBP-SDS-24 (0.99 vs. −0.72; p = 0.0072), DBP- SDS-24 (1.52 vs. −0.44; p = 0.0114), MAP-SDS-24 (1.77 vs. −0.13; p = 0.0040) were demonstrated in ABPM. Significant differences for either day or night measurements in SBP, DBP, MAP and DBP load (39 vs. 21%; p = 0.0154) were also found in ABPM, respectively. DBP and 24 hrs MAP correlated significantly with serum creatinine and cystatin C levels.

Conclusions: Hypertension was found as one of the most important factors responsible for LVH in studied children with CKD. ABPM and echocardiography regularly performed should become clinical routine in management and follow-up of these patients.

PS3-SAT-307

Urinary tract infections in preterm infants

H.Ozdemir¹, T.Ozdogan¹, A.Memisoglu¹, H.Bilgen¹, N. Yildiz* ², H.Alpay², E.Ozek¹

¹Marmara University Neonatology Department, Istanbul, Turkey, ²Marmara University Pediatric Nephrology Department, Istanbul, Turkey

Aim: The aim of this study was to evaluate preterm infants with urinary tract infection (UTI).

Method: Forty four preterm infants with UTI were evaluated for clinical and radiological findings, causative microorganisms and recurrence rate retrospectively, between 2004 and 2010. Demographic data of all infants were recorded. UTI was defined as the growth of the microorganism over 10000 c.f.u/mL in the catheterized urine specimen. Nosocomial UTI was defined as a positive urine culture detected 48 h after admission to NICU (group 1) while babies without a history of hospitalization were accepted as community-acquired UTI (group 2). Patients were initially treated with broad spectrum antibiotics which were changed according to their antibiograms. Renal ultrasonography was performed in all cases, while voiding cystoureterography (VCUG) and dimercaptosuccinic acid scan (DMSA) was performed in 59% of the cases. SPSS 17,0 was used for statistical analysis.

Results: The median birth weight and gestational age of group 1 and 2 were 1145 g (630–3600) vs 1600 g(910–2500) and 30 weeks(24–36) vs 31.5 weeks(28–36), respectively. Median gestational age and birth weight of babies in group 1 were significantly lower (p < 0.05). Nosocomial UTI was detected in 68% whereas community-acquired UTI was diagnosed in 32% of the cases. The leading causative microorganisms were K.pneumonia (40.6%) and E. coli (66.6%) for group 1 and 2, respectively. Abnormal ultrasonography was detected in 28% of the patients. Vesicoureteral reflux was detected in three infants (group1, n: 1, group2, n: 2) by VCUG. One infant in group 2 had bilateral renal scar on DMSA scan. The recurrence rate was 34% in the first year.

Conclusion: In our series E. coli and K.pneumonia were the predominant bacteria in community-acquired and nosocomial UTI, respectively. As the reccurence rate is high in preterm babies, close follow-up is necessary.

PS3-SAT-310

Measurement of pulse wave velocity in healthy youngsters—reference values and comparison of three devices

E. Kis* ¹, O.Cseprekal¹, A. Kerti¹, A.J. Szabo¹, A.Benetos¹, T.Tulassay¹, P.Salvi^2,3, G.S. Reusz¹

¹1st Department of Pediatrics, Semmelweis University, Budapest, Hungary, ²Department of Internal Medicine and Geriatrics, INSERM U961, University of Nancy, France, ³Department of Internal Medicine, University of Bologna, Italy

Objective: Carotid-femoral pulse wave velocity (cfPWV) is an established method for characterizing aortic stiffness. Normal PWV values for the pediatric population derived from large data collection have yet to be available.

Aims: (a) first to create a database and to characterize the factors determining PWV in children and teenagers. (b) Secondly to evaluate the comparability of cfPWV measurement by oscillometry (Vicorder) with applanation tonometry (PulsePen, Sphygmocor)

Patients and methods: a) cfPWV was measured by applanation tonometry. Reference tables from cfPWV obtained in 1008 healthy subjects were generated by a maximum-likelihood curve-fitting technique (LMS) Effect of gender, age, height, weight, blood pressure and heart rate on PWV was assessed. b) cfPWV was measured in 98 children and young adults (age: 17.2(5.3) years) with the three devices under standardized conditions.

Results: a) gender specific reference tables for age and height were generated. By multiple regression analysis, age, height and blood pressure remained major predictors of PWV. b) PWV by Vicorder was significantly lower than by Sphygmocor and PulsePen. There was no difference following path length correction of the Vicorder measurement, (PulsePen: 6.12(1.00), Sphygmocor: 5.94(0.91), Vicorder: 6.14(0.75) m/s). Velocities measured by the three devices showed highly significant correlations. Bland-Altman analysis revealed excellent concordance between devices. However, there was a small but significant proportional error in the Vicorder measurements showing a trend towards lower PWV by Vicorder at higher PWV values.

Conclusion: This study is the first to provide LMS reference tables for PWV in children and teenagers permitting the calculation of percentiles. Our study provides data on the three most frequently used instruments in pediatrics. Following path length correction of the Vicorder, all three devices provided comparable results. The small proportional error of Vicorder needs additional technical development to improve the accuracy of the measurements.

The study was supported by OTKA-071730, TÁMOP-4.2.2-08/1/KMR-2008-0004, ETT 06-123/2009.

PS3-SAT-312

Unilateral multicystic dysplastic kidney: Cukurova experience

A.Anarat* ¹, D.A. Tuncel¹, S. Yavuz¹

¹Cukurova University, School of Medicine, Department of Pediatric Nephrology, Adana, Turkey

Unilateral multicystic dysplastic kidney (MCDK) is one of the most frequent congenital abnormalities of kidney. It is more common in boys and usually left sided. Prognosis is often excellent. The purpose of our study was to determine the characteristic features and clinical course of patients with unilateral MCDK. Data of eighty seven patients with unilateral MCDK followed in department of pediatric nephrology in Çukurova University between 1993 and 2010 have been retrospectively investigated. All patients diagnosed with ultrasonography. Seventy five (86.2%) of them were detected in-utero. DMSA was performed in 75 (86.2%), VCUG in 63 (72.4%) children. Seventeen (19.5%) had additional abnormality. Five (5.7%) of them had vesicoureteral reflux (VUR) in low grades. Eight patient (9.1%) required antihypertensive treatment. Three (3.4%) of them underwent nephrectomy due to urinary tract infection, nephromegaly and malign hypertension. Neither malignant transformation nor renal failure was observed. But further prospective trials especially assessing the hypertension in unilateral MCDK are needed.

PS3-SAT-315

Congenital anomalies of the kidney and urinary tract in Estonia in 2007–2009

I. Vainumäe* ¹, S. Kostjukovitš², A.Traat1, Ü.Toots²

¹Children’s Clinic of Tartu University Hospital, Tartu, Estonia, ²Tallinn Children’s Hospital, Tallinn, Harju County, Estonia

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) represent 20–30% of all prenatally diagnosed malformations, and account for the most cases of pediatric end-stage renal disease.

Objective: The aim of the study was to evaluate the incidence, spectrum and management of CAKUT, determine timing of diagnosis, assess the presence of urinary tract infection (UTI) and effectiveness of antimicrobial prophylaxis.

Patients and methods: The records of 125 children with CAKUT, diagnosed in 2007–2009, were retrospectively reviewed.

Results: CAKUT were diagnosed in 125 children, 82 were male. In 42% of cases anomaly was detected prenatally, in 25% on 1 month, in 22% between 2–12 months and in 11% after 1 year of life. 54% of all children had hydronephrosis, 19% cystic malformations, 9% duplex collecting system and 18% other malformations. Acute or chronic kidney failure developed in 6% of cases (8/125). US was performed in all patients, renal scintigraphy in 61%, voiding cystourethrography in 49%, intravenous pyelography in 29%, and MRI in 6% of children. 45% (56/125) of studied patients experienced UTI-s. The main etiological agent was E. coli (68%) followed by Enterococcus faecalis (15%) and Klebsiella oxytoca (6%). 73% of isolated E. coli strains (36/49) were resistant to one or more antimicrobials. Antimicrobial prophylaxis was prescribed for 42% of children. Prophylaxis following first UTI didnt prevent consecutive recurrences during 6 month observation period (OR = 2.5, 95%CI: 0.5 - 15.7; p = 0.3). Surgical intervention was applied in 24% (30/125) of cases.

Conclusions: CAKUT are more common in boys. Mostly, abnormalities were detected prenatally or in neonatal period. More prevalent anomaly is hydronephrosis. Renal failure developed in 6% of patients. About half of patients experienced UTI-s. Non-E. coli pathogenes are relatively common in this population. Large proportion of isolated E. coli strains are resistant to tested antimicrobials. Antibacterial prophylaxis didnt prevent recurrences.

PS3-SAT-316

Pseudouremia in a child with cerebral pulsy

B. Spasojević-Dimitrijeva*¹, M. Milosavljević², M.Petković³, S.Dučić⁴, Ž. Stevančević⁵, Z. Krstić1, M. Kostić¹, I. Ivanišević¹, A. Peco-Antić1

¹University Children’s Hospital, Nephrology Department, Belgrade, Serbia, ²University Children’s Hospital, Urology Department, Belgrade, Serbia, ³University Children’s Hospital, Department of Anesthesiology, Belgrade, Serbia, ⁴University Children’s Hospital, Orthopedic Department, Belgrade, Serbia, ⁵University Children’s Hospital, Radiology Department, Belgrade, Serbia

Objectives and study: Spontaneous rupture of urinary bladder is an uncommon condition, and if occurs intraperitoneally, may be presented with laboratory signs of renal failure. Absorption of urine across the peritoneal membrane results in increase of serum creatinine level, but is associated with normal GFR.

Methods: We reported a case of spontaneous urinary bladder perforation in a 7 year old girl with cerebral palsy, who presented with abdominal pain, ascites, anuria and laboratory signs of renal failure. Two days before admission she started complaining of abdominal pain and stopped urinating. Clinical examination revealed asthenia, severe dehidration, and abdominal distension. Ultrasound pointed out a significant collection of intraabdominal fluid.

Results: Peritonitis due to perforative appendix associated with signs of renal failure was suspected. Complete blood count showed a white blood count of 34000 cells/mm3 (92% polymorphonuclears) and a platelet count of 715000/mm3. Biochemistry was performed—sodium 155 mmol/l, potassium 8,9 mmol/l, urea 65,1 mmol/, creatinine 1115 μmol/l and C-reactive protein 24 mg/l. 2 l of hemorrhagic fluid was drained through the urinary catheter. Six hours after admission, explorative laparotomy was performed and the operative finding revealed that the tip of urinary catheter is located in peritoneal cavity, and that a small mucosal defect and 2 × 3 cm tear is present in the bladder dome. The bladder defect was repaired. Cystoscopic examination revealed narrowed urethra and extremely dilated and trabeculated urinary bladder. Serum creatinine rapidly dropped to 404 μmol/l 12 h after operation and to 68 μmol/l after 24 h.

Conclusion: Urinary bladder perforation should be considered in any case of sudden abdominal pain and ascites associated with uremia which is unexplainable by other causes. To our knowledge, this is the first case report of spontaneous bladder perforation in a case of cerebral palsy. Key words: urinary bladder perforation, reverse autodialysis, children.

PS3-SAT-317

Subclinical cardiovascular disease in children with idiopathic steroid resistant nephrotic syndrome

C. Candan*¹, N. Canpolat², S. Gokalp³, N. Yildiz¹, P. Turhan¹, M.Tasdemir², L. Sever², S. Caliskan²

¹Ministry of Health, Goztepe Training and Research Hospital, Pediatric Nephrology Unit, Istanbul, Turkey, ²Istanbul University, Cerrahpasa Medical Faculty, Department of Pediatric Nephrology, Istanbul, Turkey, ³Istanbul University, Cerrahpasa Medical Faculty, Department of Pediatric Cardiology, Istanbul, Turkey

Objectives: The aim of the study was to evaluate subclinical cardiovascular disease in children with idiopathic steroid resistant nephrotic syndrome (SRNS.

Methods: Cardiovascular assessments were made on 29 patients with idiopathic SRNS (16 boys, aged 13.0 ± 3.6 years) with normal GFR. Echocardiography was performed to evaluate left ventricular hypertrophy (LVH). Ultrasonographic examination of carotid artery was made for the measurement of intima-media thickness (IMT). Aortic stiffness was evaluated by aortic (carotid-femoral) pulse wave velocity (PWV). Control group consisted of 24 healthy children to compare the PWV of the patients.

Results: Overall duration of the disease was 4,8 years (0.6 to 15.3 years). Fourteen patients (56%) had hypertension. The mean left ventricular mass (LVM) index was 36.5 ± 9.4 g/m2.7; 10 patients (34%) had LVH as LVM index >38 g/m2.7. The mean carotid IMT and carotid IMT-SDS were 0.46 ± 0.05 mm and 2.02 ± 1.05, respectively. Fourteen patients (56%) showed increased carotid IMT. In addition, significantly increased aortic PWV was observed in the patients compared to the healthy controls (5.29 ± 0.80 m/s vs. 4.93 ± 0.40 m/s; p < 0.05).

Conclusion: Patients with idiopathic SRNS have an increased risk of subclinical cardiovascular disease; therefore it is suggested to follow-up cardiovascular disease even in patients with normal GFR.

PS3-SAT-318

Proteinuria and standardized stress tolerance test in children with renal scarring

G. Miloševski-Lomić*¹, M. Kostić¹, D. Kruščić¹, G. Vukomanović¹, O. Savić2, I. Jagličić², D. Paripović¹, B. Spasojević-Dimitrijava¹, M. Cvetković¹,A. Peco-Antić¹

¹Nephrology Department, University Children’s Hospital, Belgrade, Serbia, ²Blood Transfusion Institute, Belgrade, Serbia

Objectives and study: An exaggerated blood pressure (BP) response to exercise is independently associated with increased risk of future hypertension (HTN). Physical activity induces significantly higher proteinuria (PRT) in patients (pts) with renal scarring (RS) than in healthy children. The aims of our study were to examine the: 1. BP response during standardized stress tolerance test (STT); 2. Basal and by STT induced PRT; 3. Influence of two-month ACEi therapy on BP and PRT in pts with RS and normal global renal function (GRF).

Methods: We prospectively investigated 43 pts with RS age 2–18 years and 20 healthy children age 2–16 years. Patients were tested before and under ACEi therapy. All children undervent STT: ergocycling (modified McMaster ergocycle protocol) or running (Heart rate monitoring by CicloSport CP23). BP was measured at the beginning; at maximal exertion and at the end of STT. Five urine samples were collected: early morning; after ordinary activity; immediately after STT; two to four hours after STT; early morning urine next day. Immunonephelometric method was used to determine albumin, α1 microglobulin, ß2 microglobulin and IgG excretion.

Results: An abnormal BP response during STT had six pts before and one under ACEi therapy. Children with RS had significanty higher basal and by STT induced PRT (p < 0.01) compared to healthy children. ACEi significantly decreased (p < 0.05) the BP response to STT and PRT in children with RS. BP response on STT was in a good correlation (p < 0.05) with PRT.

Conclusions: STT is a useful screening test for the detection of cardiovascular hyperreactivity and PRT in children with RS and preserved GRF. BP during STT is in a good correlation with PRT, and could be a first sign of a chronic kidney disease (CKD) progression. ACEi reduce BP and PRT and may slow down the CKD progression in these pts.

PS3-SAT-320

Infected cysts—a frequent complication?

S.Marinova* ¹, A. Boueva¹, D. Roussinov¹, P. Miteva¹, M. Gaydarova¹, G. Zlatanova¹

¹University pediatric hospital, Sofia, Bulgaria

Introduction: Infection of the cysts is a rare complication in ADPKD. In adult patients the incidence is 0,01 episodes per patient per year. There is’t published data on the frequency in children. Ususlly Gr (−) microorganisms cause the infection. Principally the haemocultures are positive and the urocultures are negative, because the lack of communication between the cysts and the kidney pelvis.

Material and methods: In a period of two years in our clinic of pediatric nephrology and dialysis we found three cases of infected cysts in two children with ADKPD and one with infected solitary cyst.

First case: A 15- year old girl, diagnosed with ADPKD in the neonatal period was hospitalized with infected cysts of both kidneys. Despite of the antibiotic treatment she was operated and unilateral nephrectomy was performed.

Second case: A 17-years old girl with ADPKD, nephrolitiasis and autoimmune hepatitis was hospitalized because of fever, abdominal pain and asotemia. On US we found infected cysts and started treatment with ciprofloxacin i.v. Her clinical condition improved and there was no need of surgical treatment.

Third case: Six years old girl was admited with clinical, laboratory and US features of severe bacterial infection of a solitary pelvical cyst in the left kidney. After treatment with ciprofloxacin the condition of the child improved and there was no need for surgical treatment. In all cases the urocultures were sterile and the haemocultures were positive for Gr(−) flora.

Conclusions: Infection of the cysts is a rare complication in children with ADPKD and ciprofloxacin appears to be a safe and effective option for treatment.

PS3-SAT-325

Might there be an association between lamin A/C mutation and polycystic kidney disease in patients with dilated cardiomyopathy?

B. Sözeri*¹, S. Mir¹, A. Berdeli¹, N. Dincel¹

¹Ege University Medical Faculty, Izmir, Turkey

Even though DCM, and PKD are genetic inherited entities with involvement of numerous mutations. Although in both diseases associated with abnormalities in the extracellular matrix, we couldn’t explain the association of these two entities with LMNA mutations in at this time, but it could be an area of future studies.

Polycystic kidney disease (PKD) occurs as autosomal dominant (ADPKD)or recessive (ARPKD) in childhood. Anatomical manifestations are multiple cysts in the kidneys and liver, but also cardiovascular abnormalities in PKD. Dilated cardiomyopathy (DCM) is genetically heterogeneous entity, characterized by left ventricular dilatation and systolic dysfunction, constitutes a significant cause for heart failure.

Lamin A/C gene (LMNA) on chromosome 1p12 is the most significant disease gene causing DCM and has been reported. The mechanism by which LMNA mutations alter the function of the nuclear membrane and cause disease is still unclear. The laminopathies are a diverse group of diseases caused by mutations in the LMNA gene encoding the nuclear envelope proteins lamin A and lamin C. Further, LMNA is the most frequent disease gene in familial dilated cardiomyopathy (fDCM). The structural hypothesis assumes that alterations in the lamins result in impaired nucleo-cytoskeleton link and cell damage. The lamins and the nucleoskeleton are interconnected with the cellular cytoskeleton extended into the extracellular matrix. Extracellular matrix abnormalities have been found in both human and animal models of polycystic kidney disease.

We aim to analyse association LMNA gene mutation and polycystic kidney disease. Three patients with DCM were selected from within the patients diagnosed with PKD (n = 25).

The first patient was a 22 months of age girl, born from a non-consanguineous parents. During her first year of life were multiple respiratory distress attacks, admitted to our hospital with severe heart failure, metabolic acidosis and chronic renal failure(CRF) stage 4. During her follow up, supportive medical treatment was given and progressive worsening of cardiac ejection fraction was detected. Dilated cardiomyopathy (DCM) was noted at the time of 8th months of CRF,PKD diagnosis. She progressed to ESRD within 10 months. Hemodialysis treatment was initiated , by the age of 36 months , she had been gone renal transplantation from her father. She has been on immunosupressive therapy for a month. Second patient was 2.5 years old boy having non-consanguineous parents. He was admitted with heart failure and renal insufficiency. He has gone to hemodialysis treatment within the first two months of diagnosis. Third one was 2 years old boy having non-consanguineous parents. He was well with an enough cardiac functions and without any renal injury. We found no any known mutations in LMNA gene, while 2 patients whose had cardiac failure (number 1and 2) had some polymorphisms.

PS3-SAT-326

The predictive value of cardiovascular biomarkers for left ventricular hypertrophy in paediatric patients with pre-dialysis CKD stages 3–5

J. Clothier*¹, J. Simpson², S. Tibby³, P. Rasmussen¹, D. Rawlins³, C. Turner⁴, R. Dalton⁴, C. Booth¹, M. Sinha¹

¹Department of Paediatric Nephrology, Evelina Children’s Hospital, Guys & St Thomas NHS Foundation Trust, London, United Kingdom, ²Paediatric CardiologyEvelina Children’s Hospital, Guys & St Thomas NHS Foundation Trust, London, United Kingdom, ³Paediatric Intensive Care Unit Evelina Children’s Hospital, Guys & St Thomas NHS Foundation Trust, London, United Kingdom, ⁴Well Child LaboratoryEvelina Children’s Hospital, Guys & St Thomas NHS Foundation Trust, London, United Kingdom

Objectives and study: Left ventricular hypertrophy (LVH) is a well recognised risk factor for future cardiovascular (CV) events in children with CKD. Our objective in this prospective study was to assess the predictive value of a novel panel of CV biomarkers for LVH in children with pre-dialysis CKD stages 3–5.

Methods: Single centre prospective study , 73 normotensive children (12.0 ± 3.2 years) mean eGFR (31.4 ± 14.8 ml/min/1.73 m²) underwent echocardiography, clinic and 24 hour BP monitoring, investigations for biomarkers, for inflammation (high sensitivity CRP [hsCRP]), arterial injury (homocysteine, uric acid, apolipoprotein B and urine protein/creatinine ratio [PCR]), ventricular load (NT-pro-BNP) and oxidative stress ADMA. Biochemical data and BP for 18 months prior to the study entry were also analysed.

Results: The mean indexed LV mass (LVMI) was 36.0 ± 8.9 g/m2, LVH defined using age-specific reference intervals for LVMI, was seen in 28 (38.4%) children. All had eccentric hypertrophy. On univariate analysis risk factors with significant relationship with LVH included systolic BP (Clinic > ABPM), body mass index, eGFR, serum calcium and dose of elemental calcium in phosphate binders. For patients with and without LVH the levels of biomarkers were (i) hs-CRP [median (IQR)], {0.57 (0.15, 1.72)vs. 0.50 (0.21, 1.33)mg/L, p = 0.13}; (ii) homocysteine (mean ± sd), {14.8 ± 7.2 vs. 13.5 ± 4.4 μmol/l, p = 0.38}; (iii) uric acid, {0.40 ± 0.10 vs. 0.40 ± 0.11 mg/dl, p = 0.99}; (iv) apolipoprotein B, {0.73 ± 0.25 vs. 0.71 ± 0.18 g/L, p = 0.72}; (v) urine PCR (n = 61), {43 (17.5, 136.5) vs. 23 (8.5, 84.0)mg/mmol, p = 0.17}; (vi) NT-pro-BNP, {15.0 (9.0, 26.3) vs. 11.0 (6.5, 16.7) pmol/l, p = 0.78}; and (vii) oxidative stress: ADMA, {700.5 ± 104.4 vs. 665.5 ± 101.8 nmol/l, p = 0.17}.

Conclusions: Our initial analysis shows that no single biomarker is predictive of LVH despite its high prevalence in this population. Multi-marker analysis may have a role in identifying those at risk.

PS3-SAT-329

Severe phenotype in an 10 years-old girl with two changes in HNF1B gene

N. Godefroid*¹, V. Guy-Viterbo¹, O. Devuyst², Y. Pirson², K. Dahan³

¹Pediatric Unit ,University Hospital St Luc, UCL, Brussels, Belgium, ²Nephrology Unit, University Hospital St Luc, UCL, Brussels, Belgium, ³Genetics, University Hospital St Luc, UCL, Brussels and IPG Gosselies, Belgium

Introduction and patient’description: Hepatocyte nuclear factor-1 beta (HNF1B) is a homeodomain-containing transcription factor that regulates tissue-specific gene expression in the kidney, liver, pancreas and gonads. HNF1B mutations lead to congenital cystic abnormalities of the kidneys and predispose the carrier to maturity-onset diabetes type 5 (1). The mode of inheritance is autosomal dominant but there is a high rate of de novo mutations. We describe a 10 years old girl who presents with two distinct HNF1B mutations. Genetic testing revealed an apparently homozygous transition C to G at nucleotide 1235 (c.1235C > G) responsible for the substitution of the highly conserved proline 412 within the C-terminal transactivation domain (p.Pro412Arg). The p.Pro412Arg is inherited from the father, known to develop impaired glucose intolerance since childhood without renal involvement.

No change has been found in the mother’s DNA, consisting with a de novo deletion of the complete maternal copy of HNF1B gene. This was further confirmed by MLPA technology. Clinically, the proband has bilateral hypodysplastic and cystic kidneys responsible for progressive renal insufficiency. She benefited from a preemptive renal transplantation at the age of 8 and developed diabetes requiring insulinotherapy during the two first years post-transplantation

Discussion: HNF1B mutations appear to be more and more implicated in renal hypodysplasia (RHD) and cystic lesions in the pediatric population, RHD being the underlying cause in more than 30% of children with chronic kidney disease. HNF1B mutations seem also to be the main cause of prenatal renal hyperechogeneity. No genotype-phenotype correlation could be established so far. The severity of the morphologic lesions and renal failure appear not different between patients with HNF1B deletions—which are frequently found, and less severe molecular alterations such as point mutations. Compound heterozygous mutations have not been reported so far. It led to a severe clinical picture in our proband.

Conclusion: We report here the first patient described in the literature heterozygous for two HNF1B changes (deletion of the whole gene and a missense mutation). This particular genotype is associated with a severe phenotype.

PS3-SAT-334

Clinical features and follow-up results of vesicoureteral reflux during childhood: analysis of 1189 cases

I. Bilge¹, A. Yilmaz*¹, S. Emre¹, A. Kiyak², O. Kizilca², H. Ander³, S. Sander⁴, O. Ziylan⁴, A. Sucu1, A. Sirin¹

¹University Istanbul Medical Faculty Pediatric Nephrology Department, Istanbul, Turkey, ²Bakirkoy Maternity and Children Hospital Pediatric Nephrology Department, Istanbul, Turkey, ³University Istanbul Medical Faculty Pediatric Urology Department, Istanbul, Turkey, ⁴Bakirkoy Maternity and Children Hospital Pediatric Surgery Department, Istanbul, Turkey

The aim of the study was to evaluate the clinical characteristics and outcome of 1189 children with vesicoureteral reflux (VUR). During 1993–2010, 1189 patients (521 male) with VUR were evaluated retrospectively. The mean age of the patients was 3.8 ± 3.5 years (0–17) at presentation, and the mean follow- up duration was 3.7 ± 2.5 years (1–12). 330 of children (27.7%) were less than 12 months old. The major reasons for initial evaluation were urinary tract infection (74%) and prenatal hydronephrosis (8.6%). VUR was bilateral in 46% of the patients. Of the 1738 renal units with VUR, reflux was grade I–II in 43%, grade III in 39% and grade IV–V in 18%. Higher grades and bilateral reflux were more common in males. Renal scarring at the time of diagnosis was observed in 19% of the renal units, and 57% of them had grade IV–V VUR. Renal scar and functional lateralization were more frequent in high grades VUR (p = 0.0001). VUR resolved in 85% of the renal units with grade I–II VUR, 62% with grade III and 18% with grade IV–V by conservative therapy, while surgical operation required in 9% in grade I–II, 17% in grade III and 64% in grade IV–V VUR. In the 291 cases (25%) with dysfunctional voiding symptoms requiring anticholinergic therapy, although the end-point was not different, VUR resolution time was significantly longer than the patients with normal bladder function (p < 0.05) . The follow-up results of our study show that even higher grades of VUR may resolve during conservative follow-up in childhood, and the final clinical course of VUR is similar in patients with or without bladder dysfunction with exception of longer resolution time.

PS3-SAT-335

Ambulatory blood pressure monitoring in adolescent obese patients with hypertension

N. Cengiz*¹, G. Parmaksız¹, E. Baskın², A. Noyan¹

¹Baskent University, School of Medicine, Department of Pediatric Nephrology, Adana, Turkey, ²Baskent University, School of Medicine, Department of Pediatric Nephrology, Ankara, Turkey

Ambulatory blood pressure monitoring (ABPM) has been increasingly used for the diagnosis of hypertension in children because it can improve the accuracy of diagnosis and may better correlate with end organ injury than office blood pressure measurement. In this study we retrospectively evaluated the records of consecutive 24 adolescent obese patients, performed in our pediatric nephrology department.

The mean age was 12.9 + 2.12 years and 8 patients were girls and 16 were boys. Six of them were prehypertensive, 12 patients were stage 1 hypertensive and 6 patients were stage 2 hypertensive. To evaluate the end organ involvement echocardiography and fundus examination are performed and microalbuminuria investigated. Echocardiography revealed left ventricular hypertrophy in seven patients and fundus examination revealed grade 1 hypertensive retinopathy in 5 patients. None of the patients had microalbuminuria. We evaluate the patients as systolic and diastolic dippers and non dippers. Twelve patients have systolic dipping pattern while 12 patients do not have. Fifteen patients have diastolic dipping pattern while nine patients do not have. There is no difference as end organ involvement between systolic dippers and non-dippers, but in the diastolic dipping group hypertensive retinopathy is statistically significantly low than the diastolic non dipping group.

In conclusion, lack of diastolic dipping is an early sign of end organ involvement. Early detection of primary hypertension is essential to prevent morbidity in later life, therefore, especially individuals with high risk such as obese adolescents should be evaluate by using ABPM.

PS3-SAT-337

Risk of urinary tract infection in children under two years of age with postnatally detected hydronephrosis

H. Flögelova*¹, J. Halek², O. Šmakal³, K. Michalkova⁴, V. Švecova⁴

¹University Hospital and Faculty of Medicine, Palacky University Olomouc, Department of Paediatrics, Olomouc, Czech Republic, ²University Hospital and Faculty of Medicine, Palacky University Olomouc, Dpt. of Neonatology, Olomouc, Czech Republic, ³University Hospital and Faculty of Medicine, Palacky University Olomouc, Dpt. of Urology, Olomouc, Czech Republic, ⁴University Hospital and Faculty of Medicine, Palacky University Olomouc, Dpt. of Radiology, Olomouc, Czech Republic

Objective: The objective was to find out if children with renal pelvis dilatation (PD) detected by postnatal ultrasound (US) screening have higher incidence of febrile urinary tract infection (UTI) in the first two years of life than those with normal US findings.

Methods: Prospective US examinations of the kidneys were performed in all 6,088 mature newborns born in the University Hospital Olomouc in the period 2005–2008. All infants with PD ≥5 mm in the transverse anteroposterior intrarenal (APIR) view were followed. This group of 236 children was divided into 4 subgroups according to the extent of PD:

5–7 mm, 7–10 mm, 10–15 mm and ≥15 mm. The incidence rates of febrile UTI, obstructive uropathy and vesicoureteral reflux were studied. Retrospectively, all the remaining infants (5,852 children with normal US findings) were evaluated for both inpatient and outpatient treatment of febrile UTI in the first two years of life. Fisher’s exact test and chi-square test were used for statistical analysis.

Results: The incidence of febrile UTI in infants with normal kidney US findings was 1.2%. Children with postnatally detected renal pelvis dilatation had statistically significantly higher rates of febrile UTI, both generally (8.90%, p < 0.0001) and in all subgroups with the exception of the greatest dilatation subgroup. Febrile UTI developed in 7.53% with APIR 5–7 mm (p < 0.0001), 8.57% with APIR 7–10 mm (p = 0.001), 20% with APIR 10–15 mm (p = 0.003) and 6.67% with APIR ≥15 mm (p = 0.238, nonsignificant difference).

Conclusions: The incidence of febrile UTI was 7 times higher in infants with postnatally detected hydronephrosis than in those with normal postnatal kidney US findings. The differences were statistically significant in 5–15 mm renal pelvis dilatation.

PS3-SAT-343

The efficacy of videourodynamic study in the diagnosis of vesicoureteric reflux

G. Parmaksız*¹, N. Cengiz¹, F. Kılınç², E. Baskın³, A. Noyan¹

¹Baskent University School of Medicine, Department of Pediatric Nephrology, Adana, Turkey, ²Baskent University School of Medicine, Department of Urology, Adana, Turkey, ³Baskent University School of Medicine, Department of Pediatric Nephrology, Ankara, Turkey

Objectives and study: The association of VUR and bladder dysfunction is well-established in children, but bladder dysfunction is frequently unrecognised and is associated with delayed VUR resolution. Accurate diagnosis of vesicoureteric reflux using clinical and laboratory parameters is often difficult in children. The aim of this study was to investigate the value of videourodynamic studies to detect VUR in children.

Methods: In this study, 118 children (86 girls, 32 boys, mean ages 8.4 + 2.9 years) with urinary tract infection and dysfunctional voiding symptoms were included. All patients were imaged by USG, DMSA scintigraphy and VCUG and underwent videourodynamic study (VUD) because of their dysfunctional voiding symptoms.

Results: VUR was determined in 150 ureters of 75 children and 101 of them were demonstrated in both techniques. In 20 ureters, VUR was shown by only VUD. The sensitivity and spesifity of VUD are 77.6%, and 81% respectively. Positive predictive value is 83%, and negative predictive value 74%. VUD revealed detrussor overactivity in 52.2%, hypocompliance in 67.7%, elevated detrussor pressure in 57.4%, detrussor sphincter dyssinergy in 3.3%, and significant residual urine in 24.5% of all patients.

Conclusions: Videourodynamic study is a reliable test to define VUR in children. This technique is superior to VCUG for diagnosis of bladder dysfunction, and can be preferred to diagnose and to follow-up VUR especially in older children with dysfunctional voiding symptoms.

PS3-SAT-344

Ventricle disfunction in juvenile-onset systemic lupus erythematosus with renal involvement

L. Sampaio¹, C. Moura², P. Costa², H. Pinto* ³, C. Afonso³, I. Brito⁴

¹Pediatric Rheumatology Unit of Hospital São João and University of Medicine of Porto, Porto, Portugal, ²Department of Pediatric Cardiology of Hospital São João and University of Medicine of Porto, Porto, Portugal, ³Pediatric Nephrology Unit of Hospital São João and University of Medicine of Porto, Porto, Portugal, ⁴Pediatric Rheumatology Unit of Hospital São João and University of Medicine of Porto, Porto, Portugal

Background: Cardiovascular morbidity and mortality, is a concerning problem in patients with Systemic Lupus Erythematosus(SLE). Juvenile SLE patients are particularly susceptible because of lengthy disease duration, and increased disease severity, namely renal involvement.

Objective: Evaluate left ventricular(LV) function in juvenile SLE and to correlate it with renal involvement.

Methods: 14 female SLE patients, with disease onset between 6 and 16 years old, and average disease duration of 6,5 years were included. Five patients had renal involvement. Using conventional echo-Doppler methods, LV diastolic function was assessed by peak velocities of early(E) and late(A) diastolic filling, the E/A ratio and deceleration time. Tissue doppler imaging included peak early diastolic annular velocity (E′) and peak late diastolic annular velocity (A′) waves. Additional parameters included E/E′ ratio, propagation velocity of the mitral valve (Vp), E/Vp ratio. LV systolic function was evaluated by two-dimensional guided M-mode tracings, to obtain ejection fraction $\left( {\left[ {\left( {{\text{LVIDd3}} - {\text{LVIDs3}}} \right)/{\text{LVIDd3}}} \right] \times {1}00} \right)$, fractional shortening $\left( {\left[ {\left( {{\text{LVIDd}} - {\text{LVIDs}}} \right)/{\text{LVIDd}}} \right] \times {1}00} \right)$. Peak systolic annular velocity of the septal wall (S) wave, isovolumic contraction/relaxation time, and ejection time were recorded by tissue doppler imaging. Renal involvement was documented by histology (WHO class IV and V).

Results: The five patients with renal involvement presented at least one criteria of LV diastolic dysfunction, while in the group of nine patients without renal involvement two had normal diastolic function. The E/A ratio and the deceleration time were abnormal in all the 5 patients. 1 patient presented impaired diastolic dysfunction, 3 presented pseudonormal pattern, and 1 patient showed restrictive pattern. The E/E′ septal ratio was normal in 4 cases. The E/Vp ratio was abnormal in 4 patients. All patients had preserved LV systolic function.

PS3-SAT-349

Is a British nice radiological guideline concerning children with urinary tract infection suitable for Oman and the developing countries?

M. El-Naggari*¹, I. Elnour¹

¹Sultan Qaboos Universty Hospital

Background: Urinary tract infection (UTI) affects 7% of girls and 1% of boys by the age of 7 years. Renal malformation could present as urinary tract infection early in childhood. In developed word renal malformation commonly detected by prenatal ultrasonography. Infants with prenatal hydronephrosis will be followed regularly and diagnosed early. In the developing countries diagnosis of prenatal hydronephrosis may only be possible at tertiary centres\’ Since 2000 children admitted to sultan Qaboos university hospital will be evaluated for renal malformation by renal ultrasound (RUS), NM Dimercaptosuccinic Acid Scan (DMSA) and voiding cystourogram (VCUG) if less than 2 years old. To evaluate whether NICE radiological guidelines is suitable for our country, we reviewed all children diagnosed as urinary tract infection seen at our hospital between the years 2004–2009.

Method: Electronic patients’ files of children diagnosed to have UTI were reviewed through the hospital information system (HIS). Incidence of malformations and renal scarring were evaluated in those with first UTI according to their age group. The number children with renal malformation who could be missed if NICE radiological guidelines were then calculated.

Results: Total of 89 children were traced through HIS with sex distribution of 8.8:1 female to male ratio 35 children (39.3%) presented with their first UTI with female: male ratio of 4.8:1.

Table 1: renal malformation detected by RUS.

Renal morphology Past history of UTI Total

No Yes

HYDRONEPHROSIS 2 9 11

NORMAL 67 98 165

PELVIC 0 1 1

SMALL 1 0 1

Total 70 108 178

Table 2: shows the frequency of Patient with renal malformation in children with first UTI in relation to age distribution.

Malformation (%) Total

age at presentation Horse shoe kidney IHN Normal PUJO VUR

0-6 months 0 1 2 0 1 4

6 months 3 year 0 0 3 0 5 8

3-5 year 1 0 6 0 3 10

5-13 year 0 0 10 1 2 13

Total 1(2.9) 1(2.9) 21(60) 1(2.9) 11(31.4) 35(100)

11 patients (31.4%) of children with first UTI were diagnosed to have VUR while 17 (48%) of 70 renal units were refluxing.16 (45.8%) patients with first UTI had scarred kidneys and 4 (5.7%) renal units had poor renal function with relative function less than 42% on DMSA, 3 of them from 3–5 years and 1 patient 5–13 years respectively.

Conclusion: Result of our data of children in younger age group les than 5 years suggest that many children with renal malformation and reflux nephropathy would have being missed if NICE guidelines were applied.

PS3-SAT-350

Nitrofurantoin: as safe as we think? Report on a drug induced hepatitis in a child on prophylactic doses

N. Granacher¹, A. Bael* ², E. Van De Vijver³

¹Department of Pediatrics, Universital Hospital Antwerp, Belgium, ²Department of Pediatrics, pediatric nephrology, Universital Hospital Antwerp, Belgium, ³Department of Pediatrics, pediatric gastroenterology, Universital Hospital Antwerp, Belgium

Purpose: Nitrofurantoin is often the drug of choice for treatment and prophylaxis of urinary tract infections (UTI) in adults and children. Severe side effects such as auto-immune hepatitis have been described in adults. Those severe side effects, as hepatitis, are uncommon in children and are never reported in children on prophylactic doses. In view of the ongoing discussion on the use of prophylactic antibiotics in children with recurrent UTI, we want to warn for the risk of severe side effects, even on prophylactic doses.

Material and methods: An eleven years old child was diagnosed in our centre with a drug induced auto-immune hepatitis, The child was taking nitrofurantoin in prophylactic doses for some months, after recurrent UTI.

Results: Discontinuation of nitrofurantoin therapy did not lead to spontaneous remission: corticoids were necessary to improve the clinical and biochemical state.

Conclusions: Nitrofurantoin, even in prophylactic doses, can cause severe liverproblems, not alone in adults, but also in children. The fact of diagnosing this problem in a child with a prophylactic low dose of nitrofurantoin, makes us wonder whether severe side-effects are underestimated. As early diagnosis results in good clinical outcome, it is crucial to further report on these side effects. The debate on the use of prophylactic antibiotics in recurrent urinary tract infection is still going on: side effects of this kind might be of influence.

PS3-SAT-352

Bioelectric impedance analysis in the diagnosis of vesicoureteral reflux

M. Torun Bayram*¹, D. Alaygut¹, M. Türkmen¹, A. Soylu¹, S. Kavukçu¹

¹Dokuz Eylül University, Department of Pediatrics, Division of Pediatric Nephrology, Izmir, Turkey

Introduction: As urine enters the ureters and renal pelvis during voiding in vesicoureteral reflux (VUR), we hypothesized that change in body water composition before and after voiding may be different in children with VUR compared to those without VUR.

Patients and methods: Children having urinary tract infections were grouped as those with high grade (≥3) VUR (Group 1) and those with low grade VUR or without VUR (Group 2). All patients were evaluated after an overnight fasting and with full bladder. Bioelectric impedance analysis (Bodystat Qudscan 4000, Bodystat Limited, British Isles) was performed before and after voiding, and the following parameters were recorded: body mass index (BMI), third space fluid (TSF) (L), change of TSF (ΔTSF), percent of total body water (TBW%), extracellular fluid (ECF%), intracellular fluid (ICF%) and percent change of TBW (ΔTBW%), ΔECF%, ΔICF%;, urine volume (mL) and urine volume/body weight (mL/kg). Group 1 and 2 were compared for these parameters.

Results: There were 14 children in Group 1, and 37 children in Group 2. Mean age in Group 1 was smaller than in Group 2 (63 ± 27 vs 90 ± 36 months, p = 0.028), but BMI was similar in these groups. While TBW% and ICF% were similar, ECF% was greater in Group 1 in both pre- and post-voiding states. However, ΔTBW%, ΔECF% and ΔICF% were not different among the 2 groups. ΔTSF was not different in Group 1 vs Group 2.

Conclusion: Bioelectric impedance analysis was not found to be useful in discriminating children with VUR.

PS3-SAT-357

Febrile urinary tract infection: what investigative protocol?

C.De Mutiis¹, C. La Scola¹, F. Mencarelli¹, M.Marsciani¹, M.V. Lega¹, A. Pasini¹, A. Costa², F. Pugliese¹, G. Montini*¹

¹Nephrology and Pediatric Dialysis,Pediatric department,S. Orsola Malpighi Hospital, Bologna, Italy, ²Pediatric DepartmenT, Univerisity of Palermo, Italy

Objective: Retrospective audit to evaluate the diagnostic accuracy and the economic and radiation cost of recent UTI guidelines, in identifying vesico-ureteral reflux (VUR) ≥ grade III and the appearance of scars at the late DMSA.

Methods: 364 children aged 2–36 months, who participated to the IRIS1 study following a first febrile UTI (BMJ 2007), were included in this audit. All children had completed the diagnostic follow-up of this RCT (ultrasonography, acute and late DMSA, cystography). The following guidelines, published after 2006, were evaluated: NICE, Cincinnati, Royal Children Hospital of Melbourne (RCH), “Top Down Approach” (TDA) and Italian Society of Pediatric Nephrology (SINP). The use of cystogram and DMSA scan is differently suggested by the various guidelines, with some being much less aggressive (NICE) while others suggesting a much wider use of radiology and nuclear medicine (Cincinnati and TDA).

Results: 30 children showed the presence of VUR ≥ III, while 44 a parenchymal scar at the late DMSA. The table shows the diagnostic accuracy and the economic and radiation cost. NICE SINP TDA RCH Cincinnati

VUR ≥ III

PPV 27,3% 13,8% 11,8% 12,5% 8,2%

NPV 94,4% 95,1% 97,2% 93,9% NC

sens. 40% 63,3% 86,7% 50,0% 100%

spec. 90,4 64,4% 41,9% 68,6% 0,0%

Scar DMSA

PPV 28,1 34,5% 27,7% NP 14,5%

NPV 88,6% 89,9% 100% NP NC

sens. 36,4% 43,2% 100% NP 100%

spec. 84,2% 86,1% 55,6% NP 0,0%

costs(€) 25198 45172 112686 23706 140476

Rad.(mSv) 111 243 743 120 905

NC = not calculable

NP = not performed

Conclusions: A perfect diagnostic protocol doesn’t exist. NICE seems to have the highest specificity and NPV with the lowest costs and radiations exposure.

PS3-SAT-364

Risk factors for vur in children with upper and lower UTI

I. Kaplan Bulut*¹, S. Mir¹, B. Sozeri¹

¹Ege University Department of Nephrology, İzmir, Turkey & Department of Pediatrics, Zeynep Kamil Maternity and Children’s Education and Training Hospital Istanbul, Istanbul, Turkey

Objectives: A total of 173 children with a first-time UTI were enrolled study. Patients with fever, elevation of acute phase reactants, low urine osmolarity, pyuria and positive urinary culture were accepted as having a upper UTI (Group1). Patients without systemical symptoms were evaluated as having lower UTI (Group 2).

Results: There were %76.8 patients with upper UTI and %23.2 patients with lower UTI. In group 1, abnormal renal US was present in 40.6% of cases while 59.4% patients had normal. Cortical defect in DMSA was detected in 61 patients (45.9%). In patients with normal renal US, DMSA revealed cortical defects in 37%. US had sensitivity 52.4% and specify 64.4% for cortical defects in DMSA. According to our criteria five variables were included in multivariate analysis: fever, elevated CRP, decreased osmolarity, fever and elevated CRP, fever + elevated CRP + decreased osmolarity. After adjustment by multivariate analysis, fever and elevated CRP (OR:1.57, 95% CI 1–2.3, P:0.01) remained associated with renal scarring. In addition, VUR was found in 63 children (54.3%). In patients with normal DMSA, MSUG revealed reflux in 32%. DMSA had sensitivity 70% and specify 70% for reflux in MSUG. Presence of cortical defect was a risk factor for VUR (OR: 5.3, 95% CI 2.4–11, P:0.00).

In group 2; renal scarring was detected in 17 patients (42.5%). US had sensitivity 53% and specificity 48% for cortical defects in DMSA. Also, US had sensitivity 50% and specificity 41% for VUR. In addition 33% of children with renal scarring and 20% of those without renal scarring had VUR. DMSA had sensitivity 62.5% and specificity 54.5% for VUR.

Conclusions: The absence of abnormal US findings in the patients does not exclude the presence of cortical defects suggestive of pyelonephritis. than protein excretion rate or uPr/uCr. More studies are needed to test its efficacy.

PS3-SAT-366

Is there a need for spect in paediatric DMSA scintigraphy?

M. Ciglar*¹, M. Poropat^1,2, D. Batinić^2,3, D. Dodig^1,2, S. Težak^1,2

¹Department of Nuclear Medicine and Radiation Protection, University Hospital Centre Zagreb, Zagreb, Croatia, ²Medical School of the University of Zagreb, Zagreb, Croatia, ³Department of paediatrics University Hospital Centre Zagreb, Zagreb, Croatia

Objectives: 99mTc-DMSA scintigraphy (DMSA) is recognised as a gold standard for kidney analysis especially for detection of possible morphology damage after urinary tract infection. There is no consensus on usefulness of single photon emission computed tomography (SPECT) in DMSA studies. The aim of this study was to compare 2 methods of DMSA scintigraphy analysis, currently used planar scintigrams and SPECT.

Methods: In 20 children (36 renal units, 4 patients with only one kidney) sequentially referred to our department for DMSA scintigraphy, 3 hours after injection of radiotracer both planar images in four projections (anterior, posterior, both posterior oblique) and SPECT were done. Each planar scintigram was analysed using filtering method developed in our department which allows better recognition of the parenchymal damage. DMSA scans (planar and SPECT) were graded as normal, pathologic with cortical defects and suspected. Results are compared and statistically analyzed.

Results: Pathological changes were detected in planar images analysed using our filtration method in 28 of 36 renal units (77%). Cortical defects were found in 12 out of 36 renal units and suspected damage in 16 out of 36. Eight out of 36 (22%) renal units had normal parenchyma. Pathological changes were detected on SPECT scintigraphy in 29 out of 36 (80%) renal units. Cortical defects were found in 9 out of 36 renal units and suspected damage in 20 out of 36. Seven out of 36 (20%) renal units had normal parenchyma. There was no statistically significant difference in two methods of DMSA scintigraphy (p = 0.39).

Conclusion: Our results confirm SPECT as equal but not superior method in DMSA scintigraphy in paediatric nuclear imaging. SPECT does not improve DMSA analysis and our results confirm its needlessness in children.

PS3-SAT-370

Renal damage in congenital single kidney

M.V. Lega*¹, C. La Scola¹, C. De Mutiis¹, F. Pugliese¹, L. Castiglioni¹, F. Mencarelli¹, A. Pasini¹, M. Marsciani¹, G. Tani², G. Montini¹

¹Nephrology and Pediatric Dialysis, Pediatric Departement, S.Orsola-Malpighi Hospital, Bologna, Italy, ²Pediatric Radology, Pediatric Departement, S.Orsola-Malpighi Hospital, Bologna, Italy

Introduction: Congenital single kidney is defined as structural or functional absence of a kidney from birth. Recently, some studies have highlighted a significant risk for these patients to develop proteinuria, hypertension and chronic renal damage, despite a long-established good prognosis.

Aim of our study: To assess the occurrence of proteinuria (Pr-U/Cr-U > 0,5 <2 years, and >0,2 for elders), hypertension (>95° percentile for age, sex and height centile) and chronic kidney damage (eGFR <90 mL/min/1.73 m²) and their risk factors in patients with congenital single kidney.

Methods and materials: Patients, aged between 0 and 18 years, with a diagnosis of unilateral renal agenesis, multicystic kidney or unilateral renal hypodysplasia confirmed by Tc-99m DMSA or Tc-99m MAG3 scintigraphy.

Results: The cohort comprised 64 children with congenital single kidney (43 boys, median age: 2 years, range: 0–14 years). The median follow-up period was 1 years (range: 0.5–18 years) and the mean exposure time to single kidney was 6 years (±4.8). Proteinuria was present in 16% of patients; febrile urinary tract infections (p .04, OR 5.25 IC 0.93–29.44) and congenital anomalies of the remnant kidney and urinary tract (p .03, OR 4.4 IC 0.83–23.7) were significant risk factors. 9% of our cohort was hypertensive, and those with genetic syndromes (p .01, OR 12.6 IC 1.28–124.51) or low birth weight (p .00, OR 38, IC 2.33–618.66) showed a higher risk. Chronic kidney failure was present in 9% of the patients, in association with posterior urethral valves (p .00, OR 14, IC 1.54–127.22) and congenital anomalies of the remnant kidney (p .02 OR 5.18, IC 0.76–35.02).

Conclusions: A significant proportion of children with a congenital single kidney develop significant renal damage. This study highlights the importance of a long-term follow up.

PS3-SAT-376

Vesico-ureteric reflux and renal scarring in children under 1 year of age with first urinary tract infection

C.W. Teoh*¹, M. Mavinkurve¹, U. Damachi¹, S. Medani¹, M. Waldron², D. Coghlan¹

¹The National Children’s Hospital, AMNCH, Tallaght, Dublin 24, Ireland, ²Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland

Objective & study: We aim to define in children <1 year with first urinary tract infection (UTI) (1) the number of lab-proven UTI, (2) the percentage with vesico-ureteric reflux (VUR) or other predisposing renal abnormality, and percentage with residual renal damage, and (3) identify a high-risk group based on disease variables.

Methods: Retrospective chart review (January 2008–June 2010) of children <1 year presenting with presumed UTI.

Results: Of the 297 children with presumed UTI, 134 were first lab-proven UTI (E. coli 133/134). 27 (20%) <3 months old, 41 (31%) 3–6 months old and 66 (49%) 6–12 months old. Average length of hospital stay was 3.24 days. Fever was most common presenting symptom (81%) followed by vomiting (42%) and poor feeding (32%). Family history of VUR was present in 11/134. Family history data unavailable in 40/134.

0f the 134, 130 (97%) had a renal ultrasound. 59 (44%) studies were abnormal. 109 (81%) had MCUG, of which 46 (42%) had vesico-ureteric reflux (20 unilateral, 26 bilateral); 18/46 (16%) had grade IV–V VUR (7 children <3 months, 4 children 3–6 months and 7 children 6–12 months). 11/18 (61%) had correlating ultrasound abnormalities. Total of 58 (43%) had DMSA scan. Only 3 (5%) had evidence of residual renal damage; 2 with grade IV–V VUR and 1 with low grade VUR. 30 children (65%) with VUR had no evidence of scarring on DMSA. 13 (28%) with abnormal MCUG did not have DMSA.

Conclusion: Our findings confirm a higher prevalence of high-grade VUR in children <3 months old. In those with follow up DMSA, we find a low prevalence of residual renal damage. We suggest modifying our investigation protocol to ensure appropriate investigation of high-risk children, but avoid unnecessary, costly and invasive investigations. We will present data to support a revised protocol for our patient group.

PS3-SAT-381

Determinants of subclinical organ damage in pediatric kidney transplant recipients

O. Cseprekál*¹, E. Kis¹, A. Kerti¹, T. Horváth², A.J. Szabó¹, M. Kollai², G.S. Reusz¹

¹Ist. Department of Pediatrics Semmelweis Inuversity, Budapest, Hungary, ²Clinical Experimental Research and Institute of Human Physiology, Semmelweis University, Budapest, Hungary

Increased cardiovascular (CV) risk caused by uraemic milieu decreases after kidney transplantation (Tx), however it remains even 5 fold higher than in the general population. CV mortality can be characterized by non invasive measure of arterial stiffness (Ast), an individual predictor of mortality. (Pulse Wave Velocity (PWV), distensibility (D), and Intima media thickness (IMT)) Clinical studies on arterial wall damage in kidney transplant children are sparse. The aim od the present study was to evaluate the Ast parameters and the possible pathophysiological factors responsible for impaired arterial function among kidney Tx patients. PWV, D and IMT of 24 Tx children (age: 16.6 ± 4.9 years) were measured by applanation tonometry, and carotid artery ultrasound. Anthropometric data and elastic parameters were given as SD score. Laboratory values of lipid, calcium phosphate metabolism, and renal function were also assessed at the time of measurements and retrospectively one year after Tx.

PWV SDS of Tx showed a tendency of discrete elevation (0.97 ± 0.71), IMT was above the 95th percentile (1.64 ± 1,36). D SDS was in the normal range (−0.01 ± 0.98). Compared to the controls PWV SDS showed positive correlation with creatinine, P, CaxP (r = 0.51;r = 0.4;r = 0.46; p < 0–05). Increased P, CaxP values were found in Tx children with IMT >95th percentile (0.13 vs. 2.61) one year after tx.(P 1.24 vs. 1.63 mmol/l; CaxP:3.19 vs 4.18 mmol2/l2 p = NS).

Conclusion: 4.5 years after tx, both morphological and functional changes can occur. Disturbances of calcium phosphate metabolism can enhance the progression of athero- and arteriosclerosis, thus the impairment of arterial elastic function in children with chronic kidney disease, after renal Tx.

Supported by: OTKA 71730, ETT 06-123/2009, TÁMOP-4.2.2-08/1/KMR-2008-0004

PS3-SAT-384

Home doppler blood pressure monitoring: a useful out-of-office measurement technique in infants and children

J. Clothier*¹, E. Rigby¹, M. Sinha¹

¹Department of Paediatric Nephrology, Evelina Children’s Hospital, Guys and St Thomas’ NHS Foundation Trust, London, UK

Objectives and study: The diagnosis and management of hypertension in infants, young children and those with learning difficulties remains challenging. ABPM is unsuitable in the youngest and may not be tolerated by those with learning difficulties. We have recently commenced home doppler BP monitoring (HDBPM). Our objectives were (i) to describe our initial experience with parent performed HDBPM (ii) to evaluate its usefulness in the diagnosis and monitoring of hypertension.

Methods: All children evaluated with HDBPM over a 12-month period were included. Parents were taught to measure systolic BP using a doppler instrument. Written instructions and a diary to record BP values were provided. Triplicate measurements twice daily for 4 weeks were requested.

Results: 15 children (12 boys) underwent HDBPM, median (IQR) age was 2.2 (0.9, 3.7) years. Of the three children aged >5 years, two had failed to tolerate 24-hour ABPM and the third judged unsuitable because of frequent seizures. Six patients were referred for confirmation of hypertension and nine for monitoring of BP control whilst on anti-hypertensive medication/s. HDBPM was performed successfully in all 15 and none required hospital admission for BP management. All six referred for confirmation of hypertension were found to be normotensive. Of the nine referred for monitoring five had normotension (three weaned and stopped and one reduced medication) and four hypertension (all four had increase in medication). All achieved target BP levels with on-going HDBPM. Detailed analysis of BP records in 10 patients showed a mean ± SD of 23 ± 13 successful measurements per week.

Conclusion: Parent performed HDBPM is feasible, provides large number of measurements and a suitable option for investigating and monitoring BP in those found to be unsuitable or intolerant to APBM. Its wider clinical applicability needs to be explored in larger prospective studies.

PS3-SAT-391

The voiding school: an effective treatment fot therapy resistant bladderdysfunction

E. Snauwaert*¹, C. Renson¹, J. Vandaele¹, A. Raes¹, P. Hoebeke¹, E. Van Laecke¹, A. DeGuchtenaere¹, J. Dehoorne¹, R. Mauel¹

¹UZ Gent, Gent, Belgium

Patients with LUTS symptoms, resistant to conventional ambulatory therapy (urotherapy, alarm, physiotherapy, anticholinergics and neurostimulation) are a hardcore group, where no further EBM options are left.

Objectives: Retrospective evaluation of the effectiveness of voiding school in children with refractory bladder dysfunctions and/or incontinence = a multidisciplinary inpatient bladder training program (2 times 5 days) consisting urotherapy, psychology, pelvic floor therapy, uroflow biofeedback.

Methods: Population n = 380, 4,7 and 17,9 y. Registration of LUTS characteristics at screening, prior to intake and follow up 12 month.

Results: When comparing voiding scores of urge syndrome at completion and 3,6 & 12 months after voiding school with the voiding scores at the entry of voiding school, a highly significant improvement of the voiding scores are demonstrated, at both daytime incontinence as enuresis (p < .0001). The estimate improvement, corrected for various variables, account for respectively daytime incontinence and enuresis: 16,5%/12,8% improvement at completion voiding school, 31,0%/24,7% 3 months, 37,2%/35,3% 6 months and 36,9%/37,3% 12 months after voiding school. Statistical analyzes demonstrated that the outcome of voiding school is depending on sex (t(1429) = −0.62, p = 0.5360), age t(1429) = 4.93, p < .0001), and nocturnal polyuria (t(1027) = −3.59, p = 0.0003). The duration of the ambulatory treatment and the presence of psychiatric co-morbidities do not affect the outcome of voiding school at both frequency of daytime incontinence, enuresis and maximal voiding volume.

Conclusions: Voiding school is a successful strategy for children with therapy-resistant bladder dysfunctions and/or incontinence, resulting in an improvement of daytime incontinence and enuresis and an increase in maximal voiding volume. This retrospective research demonstrated additional that the outcome of voiding school is being influenced by sex, age and nocturnal polyuria. Although this inpatient training program is a time-consuming and expensive treatment option, it is a considerable good option for children with refractory bladder dysfunction.

PS3-SAT-397

Renal function follow-up, using cystatin C, in patients prenatally diagnosed with CAKUT

P. Parvex*¹, C. Combescure², J. Birraux³, M. Rodriguez⁴, A. Wilhelm-Bals¹, E. Girardin¹

¹University Children’s Hospital, Pediatric Nephrology, Geneva, Switzerland, ²University Children’s Hospital, Pediatric Nephrology, Division of Clinical Epidemiology, Geneva, Switzerland, ³University Children’s Hospital, Pediatric Surgery, Geneva, Switzerland, ⁴University Children’s Hospital, Pediatric Research, Geneva, Switzerland

Objectives and study: Congenital abnormalities of the kidney and urinary tract (CAKUT) account for 20% of all significant anomalies detected on prenatal ultrasound. Despite this frequent occurrence, no reliable method to measure renal function (RF) is validated in neonates. Cystatin C (CysC) has been proposed to be an accurate renal marker for the neonatal period. The aim of this study was to assess long term RF prospectively from birth in neonates prenatally diagnosed with CAKUT.

Methods: Among 47 neonates with CAKUT diagnosed prenatally, 21 patients (pts) with severe kidney malformation (KM) had renal function follow-up with the measure of CysC and creatinine on the same day. Median follow-up was 235 (137–739) days. KM diagnoses were: 12 pelvic dilatations >10 mm; 5 hypo-dysplastic or ectopic kidney (2 withTCF2 mutation); 3 urethral valves; 1 uretherocele; 1 megabladder. 6 pts underwent interventions. One patient was started on dialyses and excluded from analyses. Factors influencing CysC were analyzed performing a linear mixed model to take into account the repeated measures.

Results: In our 20 pts, CysC values decreased rapidly in the first month (M) (16.2%) p < 0.001), significantly slower between 1 M and 1 year (y) (3.9% per month, p < 0.001) and stabilized after 1 y (0.2% per month, p = 0.83). CysC values were significantly increased in pts with bilateral KM compared to pts with unilateral KM (p = 0.02) and in TCF2 pts (p = 0.002) compared to the other pts of the KM group. The decrease of CysC over time was less marked in pts with bilateral KM (p = 0.04) and in TCF2 pts (p < 0.001). Creatinine decreased with age, rapidly during the first M (p = 0.0001) and then stabilized.

Conclusion: Assessing renal function with CysC, since birth, in neonates diagnosed prenatally with CAKUT, the RF follow-up, showed a worse prognosis in patients presenting bilateral kidney malformations or TCF2 mutation.

PS3-SAT-404

Liddle syndrome: the first family with proven mutation (PRO618SER) in the southeastern Europe

R. Bogdanović*^1,2, V. Kuburović¹, N. Stajić¹, S. Mughal³, A. Hilger³, J. Košutić^1,2, S. Ninić¹, S. Prijić¹, V. Vukomanović^1,2, M. Ludwig³

¹Institute of Mother and Child Healthcare of Serbia, Belgrade, Serbia, ²University medical School-Department of Pediatrics,Belgrade, Serbia, ³University of Bonn, Institute of Human Genetics, Bonn, Germany

Objectives and study: To present a boy with severe hypertension (HT) in whom clinical diagnosis LS was confirmed by mutational analysis and led to unraveling the etiology of treatment-resistant HT in his mother and uncle.

Methods: Standard clinical protocols were used in evaluating HT; coding sequences of exons 12 of the SCNN1B and SCNN1G genes were analyzed.

Results: Proband is the 13-yr old asymptomatic boy referred for evaluation of HT. He was found to have severe HT (170/106 mmHg) with left ventricular hypertrophy, low-normal PRA (0.27 ng/ml/h; nl: 0.2–2.8), and low plasma Ald (13.2 ng/l; nl: 42–201.5), all other findings were normal or negative. Mutational analysis showed heterozygous mutation c.1852C > T (p. Pro618Ser) in the exon 12 of the SCNN1B gene. Family history: proband’s brother and maternal grandfather both suddenly died at the 16 or 28 year of age, respectively from “heart stroke” without prior symptoms; mother (34 yrs) and uncle (32 yrs) had resistant HT since their 30s or 20s, respectively, complicated by hypertensive crisis in uncle; twin-sister is healthy, with normal BP. Proband’s mother also had lower PRA (1.4 ng/ml/h) and low serum Ald (4.2 ng/l), accompanied by hypokalemia (3.0 mmol/l) and metabolic alkalosis (pH 7.47, BE 3.5 mmol/l). Pro618Ser mutation was found in both proband’s mother and uncle, whereas the sister had wild type SCNN1B gene. Amiloride and strict salt restriction led to normalization of BP both in proband and his mother, the same treatment was advised to proband’s uncle.

Conclusion: Positive family history, lower PRA and very low serum Ald level were the clues for clinical diagnosis of LS, confirmed by genetic analysis which enabled institution of rationale and effective treatment. To the best of our knowledge, this is the first report of LS in the Southeastern Europe, confirmed by genetic analysis.

PS3-SAT-409

Ultrasound imaging in long-term follow-up after nephrectomy in children treated for kidney tumor—preliminary study

A. Moczulska*¹, S. Szymik-Kantorowicz², K. Zachwieja¹, M. Miklaszewska¹, J.A. Pietrzyk¹

¹Department of Pediatric Nephrology, University Children’s Hospital of Cracow, Poland, ²Pediatric Surgery Department University Children’s Hospital of Cracow, Poland

Objectives and study: The aim of the study was to assess the long-term effects of nephrectomy using ultrasound imaging in patients treated in their early childhood for kidney tumor. The study group consisted of 23 patients-12 girls and 11 boys, 7–17,5 years old(mean 11,8 yrs), minimum 5 to 12,5 years (mean 8 yrs) after completed chemotherapy for nephroblastoma. The kidney tumor was diagnosed at the age of 2 months-9 years (mean 3 yrs). After initial chemotherapy unilateral nephrectomy was performed with continuation of therapy 1–10 (mean 5,7) months.

Methods: The clinical and biochemical assessment was performed including renal ultrasound with doppler to evaluate renal flow and resistive index (RI). Common carotid intima-media thickness (cIMT) was measured and correlated with 24 h ABPM measurement. GRF was calculated with Iohexol method.

Results: Hyperfiltration with GRF >120 ml/min/1.73 m² was measured in 5 children aged 7–14 (mean10 yrs). CKD stage 2 was diagnosed in 4 patients aged 11–14 (mean12,6 yrs) and in 2 of them proteinuria was observed. Microalbuminuria appeared in 1 patient in concomitance with hypertension, increase of RI and cIMT value. ABPM showed hypertension in 6 children. RI >0,7 was found in 4 patients, and correlated with high cIMT and blood pressure values in 2 cases. Increase of cIMT was seen in 6 patients (26%). Increased plasma renin activity measured in 2 children correlated with renal hyperfiltration.

Conclusions: Abnormal (increased or decreased) kidney function in long-term follow-up was diagnosed in 39% of patients (n = 9) after treatment for kidney tumor. Special ultrasound imaging of kidney and vasculature seem to be useful methods to detect late complications in these group, which may require treatment. Further studies are needed to work out recommendations for intensifying long-term care in these patients.

PS3-SAT-416

Is it necessary to perform voiding cystourethrography (VCUG) in every child with acute pyelonephritis (APN)?

T. Jarmoliński*^1,2, S. H. Marciniak¹, B. Pacanowska¹, G. Dudarenko³

¹Department of Pediatrics, Nephrology and Toxicology, District Children’s Hospital, Szczecin, Poland, ²Department of Pediatrics, Hematology and Oncology, Pomeranian Medical University, Szczecin, Poland, ³Department of Radiology, District Children’s Hospital, Szczecin, Poland

Objetives: To analyse incidence and type of urinary tract abnormalities diagnosed on VCUG in children with APN and estimate a role of urinary tract USG and DMSA renal scan in establishing indications for VCUG.

Methods: Between 2000 and 2010 VCUG was performed in 1082 children after APN (654 female and 428 male, aged 1 mo—17 year).

Results: Abnormalities were found in 211 cases (19,5%; 134 F, 77 M): vesico-ureteral reflux (VUR) in 200 (18,5%; 129 F, 71 M) and bladder and/or urethra defects in 11 (1,0%; 5 F, 6 M). High-grade VUR (IIIo -Vo) was diagnosed in 125 cases (11,6%) and low-grade in 75 (6,9%). Among high-grade VURs 65 (52,0%) were bilateral (at least IIIo VUR on one side) and 60 (48,0%) unilateral. In low-grade group most VURs were unilateral (56 cases, 74,7%); only 19 (25,3%) were bilateral. Total number of 284 refluxing units were diagnosed: Io - 41 (14,5%), IIo – 66 (23,2%), IIIo −119 (41,9%), IVo – 50 (17,6%) and Vo - 8 (2,8%). Among children with abnormal bladder and/or urethra bladder diverticula were diagnosed in 5 cases, dilatation or narrowing of urethra in 4, bladder neck dilatation in 1 and bladder diverticulum with posterior urethra dilatation in 1. Incidence of significant urinary tract abnormalities diagnosed on VCUG was 12,6%. Comparing frequency of abnormal result of USG and/or DMSA scan in groups of children with VUR, with high-grade VUR and without VUR more frequent appearance of abnormal USG and/or DMSA was found in group with VUR and high-grade VUR (USG + DMSA—22/107 and 16/63 vs 42/366, p < 0,05; USG—76/142 and 50/90 vs 228/615, p < 0,05; DMSA—38/115 and 28/66 vs 87/431, p < 0,05).

Conclusions: VCUG seems to be not necessary in every child with APN. It is particularly indicated in patients with abnormal USG and/or DMSA scan.

PS3-SAT-420

Bladder control training in children with dysfunctional elimination syndrome

A. Peco-Antić*^1,2, D. Paripović ², S. Trojanović², D. Mandžukić², I. Ivanišević²

¹Medical Faculty of University of Belgrade, Belgrade, Serbia, ²Nephrology department, University Children’s Hospital, Belgrade, Serbia

Bladder control training (BCT) involves a combination of cognitive, behavioral, physical and pharmacological therapies. From recently, pelvic floor biofeedback (PFC) using auditory-visual signals as a part of a computer game to understand, and than change the dynamics of voiding and sequential muscle group acitivity, has been promising BCT.

Objective: To evaluate the efficacy of BCT for achieving resolution of dysfunctional elimination syndrome (DES).

Material and methods: From 2008 to 2010, all girls with DES treated by BCT were recruited to participate in the study. The screening consisted of history, clinical examination, neurological and psychological screening and uroflowmetry, followed by ultrasonography of the urinary tract. Patients with complex urinary tract abnormalities as well as those unable to fully cooperate, were excluded from the study. Urinary and bowel incontinence and withholding was scored by SDES (ascending score, 0 = normal). BCT consited of conservative training programme and biofeedback sessions of uroflowmetry and PFC with comuter games (3 per week) during 2 months. BCT results were documented by SDES, character of voiding and electromyography curve (EMG), post-void residual (ml) and patients and parenteral satisfaction.

Results: Sixty-three girls, median age of 9 years (interquartile range, IQR 7–10) with median SDES of 3 (IQR, 1–6) were included in the study. Majority of the patients had recurrent UTI (73.0%), abnormal voiding curve (VC, 69.4%), increased post-void residual (PVR, 55.5%), and bladder wall thickened (BWT, 50.8%). BCT achieved significant decrease of SDES (3 vs 0), EMG (52.4% vs 34.9%) and post void residual urine (16.1 vs 11.5), while decrease of abnormal VC (68% to 39%) didn’t reach statistical significance. After a mean follow-up of 6 months, most of parents (85%) expressed satisfaction with BCT.

Conclusion: BCT is effective in children with DES and/or recurrent UTI. PFC is important component of BCT.

PS3-SAT-421

Paediatric renovascular hypertension related to fibromuscular dysplasia: a multisite involvement study

F. Bandin*¹,T. Kwon², S. Decramer¹, G. Deschenes², A. Dallocchio

¹Paediatric Nephrology and Internal Medecine, Children Hospital, Toulouse, France, ²Paediatric Nephrology, Hopital Robert Debré, Paris, France

Background: Fibromuscula dysplasia (FMD) is a well-known cause of HTA, but less is known about circumstance of diagnosis, natural course and evolution after renal angioplasty.

Methods: Multicentric study (2 centre, 30 patients) including patients with HTA related to renal arterial stenosis.We reviewed circumstances at diagnosis of hypertension, imaging studies, disease course, medical treatments and need for angioplasty. Efficacy of angioplasty could be evaluated on immediate criteria such as per-endoscopic evidence for residual stenosis and rapid decrease in anti-hypertensive treatments but also on long term criteria such as evolution of renovascular lesions and need to maintain or increase antihypertensive therapies.

Results: Among the patients, twenty of them presented with primary FMD which could be classified in sporadic FMD in 17 cases and in familial FMD in only three cases. A syndromic FMD could be noted in ten cases.Clinical symptoms at diagnosis were mainly aspecific. Extra-renal lesions at diagnosis were noted in twelve patients. Twenty-four patients underwent an angioplasty.Among them, immediate per-operative findings revealed complete efficacy (no residual stenosis) in nine patients, persistent residual stenosis in eleven patients and failure of angioplasty in two patients. No per-operative findings could be retrieved from archives for two patients.Evolution of renal lesions after angioplasty (AP) showed no restenosis for 7 patients and progressiv recidivism of stenosis for two patients. Among patients with residual stenosis post first-AP, vascular intervention was needed for six patients (2 surgery, 4 AP). An efficacy in withdrawal of anti-hypertensive\’s treatments, described as possibility of tapering off at least one treatment, could be noted in the immediate post-AP period (firdt month) for nine patients. Among the 22 patients that could be followed after AP, efficacy of this intervention could be noted at last follow-up in seven patients and all treatment could be stopped for 4 patients. Among patients who underwent a second angioplasty (n = 7), no efficacy could be seen? Two patients underwent a third angioplasty without significant results. Among patients who underwent an angioplasty for a rena arterial stenosis, seven of them also had vascular renal lesions that didn\’t required at first endovascular treatment. Evolution of these specific lesions showed stability (n = 2), aggravation with vascular intervention (n = 2) and no possibility for intervention in 3 patients. Secondary onset of another progressive renal stenosis was seen in one patient.

Conclusion: Efficacy of angioplasty could be seen in one third of the patients. No significant improvement could be seen neither after performing a second nor a third angioplasty in the patients of the series. However, for patients whom didn\’t experiment benefits from first and/or other angioplasties, this intervention couls have played a role in stabilizing residual stenosis and/or blood pressure numbers.

PS3-SAT-425

PSA-NCAM expression in human fetal and neonatal kidney

S. Cirovic*¹, J. Markovic-Lipkovski¹, N. Radulovic¹, R. Bogdanovic¹, J. Tadic¹, G. Mueller¹, C. Mueller¹

¹Molecular Nephrology, Kidney Development, MZMF—Centrum für med. Forschung, Universitätsklinikum Tübingen, Tübingen, Germany

Objectives and study: Neural cell adhesion molecule- NCAM first describe as adhesion molecule in neural cells may carry the linear homopolymer of alpha 2,8-linked sialic acid (polysialic acid- PSA), associated with plasticity and remodeling during the development in the nervous system. NCAM is also present in fetal kidney, but it’s significantly reduced after birth. In this study NCAM/PSA-NCAM coespression as well as NCAM correlation with proliferation markers Ki-67 and stem markers CD24 in fetal and neonatal kidney has been investigated.

Methods: Human neonatal and fetal kidney tissue specimens of different stage of gestation were analyzed. NCAM- 180 kDa antibody was used for immunofluorescent analysis. Double staining of NCAM was performed with CD24, Ki-67 and PSA-NCAM.

Results: Fetal expression: NCAM-180+ cells- mesenchyme around branch of ureteric bud, nephtogenic interstitium, mesenchymal cap, pretubular aggregate, renal vesicles, comma body, proximal and medial segment of the S-shaped body, visceral and parietal epithelium; PSA-NCAM + cells- pretubilar aggregates and renal vesicles; CD24+ cells- pretubular aggregate, renal vesicles, comma body, proximal, medial and distal segment of the S-shaped body and tubuli; Ki67+ cells- pretubilar aggregates, renal vesicles, comma and S-shaped body, single cells in glomeruli. Neonatal tissue expression: NCAM-180+ cells- in small areas in interstitium, these areas expressed also very rare cells PSA-NCAM+; CD24+ thin limb and single glomeruli cells; Ki67+ rare single cells in cortex and medulla.

Conclusion: During fetal development NCAM expression completely despaired from all epithelial structures and only small number of interstitial cells keeps expression. Early induced epithelial aggregates show presents of all tested markers, suggesting that PSA-NCAM expression on these structures could be relevant for inhibition of adhesion forces between progenitor cells, and that NCAM molecules required polysialylation as a trigger for proliferation, differentiation and for mesenchymal-epithelial transformation of renal progenitors.

PS3-SAT-427

Metabolic risk factors evaluation in children and adolescents with hypertension

M. Šubat-Dežulović*¹, A. Brajdić^2, S. Flajšman-Raspor¹

¹Department of Pediatric Nephrology, Clinical Hospital Centre, Rijeka, Croatia, ²Clinical Hospital Centre Rijeka, Rijeka, Croatia

Objective: The combination of hypertension, abdominal obesity, dyslipidemia and hyperglycemia is referred as metabolic syndrome (MeS).

Aim of our study: Was to asses the presence of MeS in children and adolescents that were evaluated for hypertension.

Patients and methods: 77 selected children and adolescents with primary hypertension were retrospectively evaluated for MeS based on criteria published by International Diabetes Federation. We focused on the presence of obesity expressed by body mass index (BMI), abnormal serum lipids (triglycerides ≥1.7 mmol/L) and low high-density lipoprotein cholesterol (HDL-cholesterol ≤1.03 mmol/L in males and ≤1.29 mmol/L in females), high serum glucose (≥5.6 mmol/L) and hypertension (systolic and/or diastolic blood pressure ≥95th percentile adjusted for height, age and gender).

Results: 77 selected children and adolescents (64 males, 13 females), aged 8 to 18 years, with excluded secondary causes of hypertension represent the study group. 36 (47%) children had BMI >95th percentile for age, 20 (26%) had BMI 80 to 95th percentile, 8 (10%) had BMI 50 to 80 percentile, while only 13 (17%) patients had BMI less than 50 percentile. Hypertriglyceridemia was found in 17 patients including 11 (31%) of 36 patients with BMI >95 percentile. Low HDL-cholesterol had 14 patients including 9 (25%) of 36 obese patients. Impaired glucose tolerance had 15 patients including 11 obese patients.

Of total, 59 patients were classified as hypertensive, 13 as prehypertensive while 5 had normal blood pressure. Seven of 36 obese and hypertensive patients had all three metabolic risk factors while 4 with one or two risk factors were prehypertensive. In total 11 patients fulfilled the criteria suggestive of MeS.

Conclusions: Although there is no clear definition of MeS in children, the results of this study suggest that metabolic risk factors are clustering in children and adolescents with hypertension.

PS3-SAT-429

A ten-year-old girl with hypertension—case report

A. Szmigielska*¹, M. Roszkowska-Blaim¹, H. Kamińska², B. Werner²

¹Department of Pediatric Nephrology, Warsaw Medical University, Warsaw, Poland, ²Department of Pediatric Cardiology and General Pediatrics, Warsaw Medical University, Warsaw, Poland

Hypertension occurs in 2–5% children and may be primary or secondary. The differential diagnosis is broad, but sometimes we can make a diagnosis after physical examination. A ten-year-old girl was admitted to the hospital because of hypertension. Elevated blood pressure was diagnosed in routine physical examination one month before. Until hospitalization she was completely health. There was no family history of hypertension and renal diseases. On physical examination patient was alert, height - 136 cm (25—50 pc), weigth—26.5 kg (3–10 pc), the pulse – 88/min, the blood pressure measured on upper limbs was 145/90 mmHg and 120/70 mmHg on lower limbs. There was no skin changes. Cardiac examination reaveled regular heart rate and systolic ejection murmur (2/6 Levine scale) over anterior part of the chest radiating to the back. There was no palpable pulse on femoral arteries. The abdomen was soft and there was no hepatosplenomegaly. Laboratory values of blood and urinanalysis were normal. Plasma renin activity and thyroid hormones were normal. A 24-hour urine collection for catecholamines was negative. Systolic and diastolic hypertension was detected in 24-hour Ambulatory Blood Pressure Monitoring. A renal ultrasonographic examination showed unilateral renal agenesis. Chest radiography reaveled typical changes in ribs due to erosion by collateral vessels. Hypertrophy of left ventricular and coarctation of aorta was detected in echocardiography. The peak gradient was 65 mmHg. Angio-CT showed significant aortic coarctation with very narrow isthmus (1,8 mm) and numerous massive collateral vessels. The girl was treated with calcium-channel blockers and she was qualified to surgery procedure—stent implantation. “Adult-type” of coarctation can be asymptomatic until adulthood. Untreated coarctation of aorta can lead to severe complications in future especially in patients with unilateral renal agenesis.

PS3-SAT-431

Long-term follow-up of pediatric patients with acute renal failure after cardiac surgery

J. Louw*¹, D. Mekahli², R. Lombaerts², E. Levtchenko², B. Cools¹, R. Heying¹, B. Eyskens¹, M. Gewillig¹

¹Pediatric Cardiology, University Hospitals Leuven, Leuven, Belgium, ²Pediatric Nephrology, University Hospitals Leuven, Leuven, Belgium

Background: Acute renal failure(ARF) in the immediate postoperative period after cardiac surgery requiring extracorporeal circulation(ECC) is frequently described. Long term outcome in the pediatric population is not well known.

Methods: We retrospectively reviewed 1407 pediatric cases(age <16 years) who underwent cardiac surgery requiring ECC from 1998–2008. ARF was defined as a creatinine value above twice the normal value for age occurring within the first 96 hours after surgery. All patients were screened for the presence of proteinuria and hypertension; glomerular filtration rate(GFR) was calculated using Schwartz’s formula and renal ultrasound with Doppler was performed for evaluating renal size, the aspect of renal parenchyma and renal perfusion.

Results: From 1407 patients, 117 patients(8%) had ARF after cardiac surgery. Pre-existing renal disease was found in 5 patients(4%): solitary kidney(2), multicystic dysplastic kidney(1), hydronephrosis(1), and renal dysplasia(1). Renal replacement therapy(RRT) was required in 8 patients(6.8%). Eighteen patients(15%) deceased due to multiple organ failure or sepsis as the main causes. The mean follow-up after surgery was 5.6 years(range 2.1–11.3). Of subjects requiring dialysis during the immediate postoperative period, none remained on RRT during follow-up. In 10 patients(19%) decreased kidney size was noted(SD <−2 for age). Six patients(10%) were hypertensive and required anti-hypertensive treatment. Renal artery stenosis was excluded in all patients. Chronic kidney disease(CKD) was noted in 17 patients(32%), 3 patients with stage 1, 12 patients had stage 2 CKD, and 2 patients stage 3 CKD. Eight patients(47%) had proteinuria, and 8(47%) patients demonstrated an increased corticomedullary reflectivity on renal ultrasound.

Conclusions: In our cohort acute renal failure in the immediate post-operative period after pediatric cardiac surgery occurred in 8% and led to chronic kidney disease in 1/3 of these patients. Long-term nephrologic follow-up is warranted in this patient population.

PS3-SAT-433

Evaluation and follow-up of children with fetal hydronephrosis

S. Flajšman-Raspor*¹, M. Šubat-Dežulović¹

¹Department of Pediatric Nephrology, Clinical Hospital Centre, Rijeka, Croatia

Aim of the study: The purpose of this study was to report the outcome of children identified by fetal ultrasonography (FUS) as having potential urologic anomalies.

Materials and methods: We retrospectively analyzed a group of 140 children, 41 (29%) girls and 99 (71%) boys in whom FUS was indicative for potential urologic anomalies. In all of them besides sonographic follow-up, vesicoureteral reflux (VUR) was investigated by voiding cystourethrography. Based on initial screening, radionuclide studies (MAG3 or DMSA scan) were performed. Based on results of diagnostic investigation, we listed 39 children, 12 girls and 27 boys, in whom control MAG3 scan was done to establish the potential need for surgical procedure. We evaluated differential function (DF) and diuretic washout (furosemid applied 20 minutes after MAG3 aplication).

Results: Out of 39 children, 28 (7 girls and 21 boy) had hydronephosis suggestive of pyeloureteral stenosis while 11 children with hydronephrosis had dilatation of pyelon with eventually diagnosed VUR (5 girls and 6 boys. In total, 11 children were treated surgically; 4 with obstructive dilatation of pyelon and ureter due to ureterocoela and 7 children because of pyeloureteral stenosis confirmed by obstruction on control MAG3 scintigraphy. Stenosis of pyeloureteral junction was confirmed by decline of differential function (DF) >5% and/or no diuretic washout in all. In 7 children with persistent dilatative VUR (3 girls and 4 boys) endoscopic surgery was performed. In the group of children in whom the surgical procedure was performed, as well as in children with no surgical intervention, we found improvement of DF, but it was not significant (p 0.49 and p0.43 respectively).

Conclusion: Careful follow-up, timed sonographic and scintigraphic evaluation are needed in children with potential urologic anomalies with a goal of preserving renal function and preventing the development of obstructive uropathy.

PS3-SAT-436

The relationship between blood pressure and some metabolic aspects in 14 years old adolescents—Sopkard 15 study

P. Szczesniak*¹, P. Czarniak¹, E. Krol², M. Krawczyk³, T. Zdrojewski³, B. Rutkowski², B. Wyrzykowski³

¹Department of Pediatric Nephrology and Hypertension, Medical University of Gdańsk, Poland, ²Department of Nephrology, Transplantology and Internal Diseases, Medical University of Gdańsk, Poland, ³Department of Hypertension and Diabetology, Medical University of Gdańsk, Poland

Introduction: Hypertension as a lifestyle disease is more common observed in adolescents. There are many external and metabolic factors that cad take effect on blood pressure. The aim of the study was to find any factors that may influence blood pressure level in general population of adolescents.

Material and methods: 748 children of 367 female and 381 male in the age of 14 were studied. Physical examination was proceeded including height, body mass, calculation of body mass index (BMI), skin folds and blood pressure three times measurements. Glucose, TSH, creatinine, uric acid, albumins, cholesterol, triglycerides (TG) was measured in serum and albumin concentration in urine sample. Abdominal US with measurement of abdominal fat layer was performed. Volume of a kidney and its sinus was calculated using ellipsoid formula.

Results: In the examined group we observed statistical significant difference between blood pressure and skin folds’ thickness (p = 0,001), serum uric acid (p = 0,047), serum albumin (p- = 0,0001), TSH (p = 0,005) and TG concentration (p = 0,005) . We also found relationship between blood pressure and total kidney volume (p = 0,01) and subcutaneous fat thickness (p = 0,05).

Conclusions: Blood pressure level is assessed to internal metabolic factors of nutrition status. There is an interesting observation of the relationship between blood pressure level and total kidney volume.

PS3-SAT-441

Reversible posterior leukoencephalopathy in juvenile systemic lupus erythematosus: case report

C.A. Rogow*¹, M.M. Fraga¹, S.L. Bergamo¹, M.C. Andrade¹, J.T.d A. Carvalhaes¹

¹Division of Pediatric Nephrology—Federal University of Sao Paulo/UNIFESP, Sao Paulo, Brazil

Posterior reversible leukoencephalopathy syndrome (PRES) is a rare neurological complication associated with juvenile systemic lupus erythematosus (JSLE) and its pathogenesis remains not fully understood. It consists of neurological manifestations and transient changes on neuroimaging, related to cerebral edema. We describe the case of a male adolescent with JSLE developing PRES associated with hypertension, including its clinical presentation, diagnosis and follow up. A 12-year-old male adolescent presented clinical and laboratorial history of JSLE with rapid evolution and serious complications, including renal, hematologic and infectious ones, and received various immunosuppressive drugs (corticosteroid pulse, azathioprine, cyclophosphamide, rituximab). He also developed arterial hypertension and was receiving ACE inhibitor (captopril 1,5 mg/kg/day). During hospitalization, he had an acute episode of focal neurological deficit, seizure and hypertension (blood pressure of 170 × 140 mmHg)—consisting with hypertensive encephalopathy and treated with sodium nitroprusside. Neuroimaging showed typical findings of PRES—high signal intensity mainly in subcortical white matter in occipital and parietal lobes in T2-weighted and FLAIR sequences.

In this report, as well as in literature, multiple factors may be related as etiology of PRES, including immunosuppressive therapy, lupus nephritis itself and especially hypertension. Magnetic resonance imaging (MRI) seems to be superior to computerized tomography in diagnosing PRES. The patient did not have any neurological sequelae or recurrence of episodes. As previously reported, acute hypertension is the most important triggering factor for PRES.

PS3-SAT-445

Severe hypertension associated with hypo plastic renal arteries

C. Corrado*¹, C. Canale¹, M.M. D’Alessandro¹, G. Pavone¹, M.C. Sapia¹, R. Cusumano¹, S. Maringhini¹

¹Pediatric Nephrology, “G. Di Cristina” Hospital, Palermo, Italy

Emanuele, a 7 year old patient, with a history of headache was admitted to the emergency room for an episode of absence seizure; his blood pressure was 220/180 mmHg. A brain CT showed “a hypodense area in the left parietal cortex”. On admission to the cardiology unit an echocardiogram documented a severe concentric left ventricular hypertrophy associated with a reduction of the ejection fraction. The blood pressure remained elevated 230/170 mmHg despite intravenous drug therapy with clonidine and esmolol. An abdominal CT showed \“abnormal origin of thin renal arteries”, and he was referred to our nephrology unit. On admission the child was restless and his pressure values were: 225/175 mmHg. A repeated CT brain showed a picture of \“hypertensive encephalopathy” and confirmed the presence of the hypodense area. Labetolol ev was immediately initiated, the infusion rate was increased gradually up to 1 mg/kg/h, with a progressive reduction in blood pressure (170/120 mmHg). During labetolol therapy blood pressure was 140/95 mmHg. An angiography showed that both renal arteries were of reduced size. A “stent placement” wasn’t possible, both renal arteries were thin. In the second day oral antihypertensive therapy with calcium channel blocker and alpha-beta blocker was initiated with a reduction of blood pressure to 130/90 mmHg (ABPM). The fourth day labetolol therapy was discontinued and treatment with oral clonidine (12,5 mcg/kg/die) was introduced. The patient was discharged in treatment with clonidine (15 mcg/kg/day), carvedilol (2 mg/kg/ day), amlodipine (0.4 mg/kg/day) and spironolactonum (1 mg/kg/day), his blood pressure was 126/82 mmHg (ABPM). After two months he had a normal renal function and he was asymptomatic on normal blood pressure. In conclusion this child has an anatomic abnormality of renal arteries never described before which produced severe hypertension which was controlled with several drugs.

PS3-SAT-446

Prevalence of urinary disorders in Sicilian children

R. Cusumano*¹, R. Ortolano¹, F. Leone¹, L. Belvedere², A. Lo Cascio², S. Maringhini¹

¹Paediatric Nephrology, “G. Di Cristina” Hospita, Palermo, Italy

Urinary disorders (UD) in children are often understimed by parents and paediatricians. UD can be functional and transient, but sometimes highlight malformations of the urinary tract and are often associated with urinary tract infection (UTI). To assess the prevalence of UD in children in our area (Sicily) we developed a questionnaire that has been distributed by family pediatricians to parents of children older than 5 years. The questionnaire was distributed by 15 pediatricians and filled for 306 out of 348 children. Age (mean ± SD) of children surveyed was 8.6 ± 2.7 years; age of acquisition of bladder sphincter control was 27.6 ± 8.7 months; 6,5% voided more than 7 times a day, 3,9% less than 3 times ; 15% had \“urge incontinence\”; perineal support maneuvers (PM) were reported in 22%; enuresis (ENU) was reported in 13%, diurnal incontinence (DI) in 16%. Among those with DI 48% had \“urge incontinence\”, 10% had an increased and 4% a reduced frequency of voiding. Analysis of the questionnaires in children with ENU showed that family history of enuresis was present in 38.%; ENU was monosymptomatic in 43% and in 53% was associated with DI. UTI was reported in 13% of children and 27% of them had urinary disorders (ENU in 7,3% DI in 24,4%). No correlation was found between age of sfinteric control and ENU or DI. UD in children of our area are more frequent than those reported. A questionnaire explained by family doctors and filled by parents may be useful to detect UD.

PS3-SAT-448

Prevalence of vesicoureteral reflux in Požeško-Slavonska county from 2006 to 2010

LJ. Banožić*¹, N. Ćosić¹, A. Šimić Klarić¹, V. Drkulec¹

¹General County Hospital, Požega, Croatia

Objectives and study: Vesicoureteral reflux (VUR) is characterized by the abnormal, retrograde flow of urine from the bladder back into the ureters. VUR is most commonly diagnosed in infancy and early childhood. The aim of this study was to determine the prevalence of VUR in our County in period from year 2006 to 2010.

Methods: In this retrospective study, examinees were all children with VUR diagnosed and monitored in Department of Pediatrics, who were born in Maternity Department of General County Hospital Požega, Croatia.

Results: In the period from 1st January 2006 to 31st December 2010, 3166 children were born is the Maternity Department. VUR was diagnosed by voiding cystoureterography at 37 of them, 27 (73%) girls and 10 (27%) boys. Prevalence of VUR was 1,17%. VUR was left side in 25 (67,5%) cases, right side in 5 (13,5%) and bilateral in 7 (18,9%) cases. Reflux was grade I in 6 patients, grade II in 15 patients, grade III in 14 patients and grade IV in 2 patients. The most of children (15) were diagnosed in the second year of life. Treatment was nonoperative management in 23 (62,16%) children, surgical treatment in 3 (8%) children and endoscopic injection of Deflux in 11 (29,73%) children.

Conclusions: Prevalence of reflux in Požeško-slavonska County is 1,17% which is compatible to data published in the literature. Treatment with endoscopic injection of Deflux was effective in 29,73% of children.

PS3-SAT-452

Cross-sectional ABPM study of 122 diabetic children and adolescents

P. Toth-Heyn*¹, R. Balazs¹, L. Madacsy¹, A. Korner¹

¹Ist Department of Paediatrics, Semmelweis University, Budapest

Objectives: The prevalence of hypertension is much higher in diabetic patients than in the normal population. Autonomic neuropathy is one of the known pathogenic factors, an early complication of childhood diabetes mellitus in strong correlation with metabolic control. The aim of the present study was to evaluate the prevalence of manifest hypertension and non-dipping phenomenon as a marker of autonomic neuropathy in a large cohort of type 1 diabetic children and adolescents.

Methods: Patients were enrolled during a one year study period from the largest children diabetes center of Hungary, the Ist Department of Pediatrics, Budapest (n = 122, 50 girls, mean age 15,3 ± 3,0 years). Patients were admitted for metabolic control and screening examinations. Twenty-four hour blood pressure (BP) monitoring (ABPM) was carried out and evaluated based on international multicenter results.

Results: Hypertension was detected in 26/122 patients (21%). The nocturnal BP dipping was <10% in 71/122 patients (58%). There was no difference in the prevalence of hypertension (21 vs. 22%) or non-dipping (66 vs. 44%) between the boys and girls. The average systolic BP was, however, higher in boys (117,2 ± 8,4 mmHg) than in girls (114,0 ± 8,3 mmHg), both during the day and the night. Heart rate was higher during the whole day in girls (90 vs. 81 min−1). We could not demonstrate any difference in the prevalence of hypertension according to the insulin therapy regimen. HbA1c values correlated with the 24 h and night-time diastolic BP (r = 0,31, p < 0,01), but not with the systolic BP values.

Conclusions: This is the largest published ABPM study in diabetic children and adolescents, calling attention to the high prevalence of hypertension and cardiovascular autonomic dysfunction. Our results show strong similarity to previously published results in smaller populations on the prevalence of diabetic hypertension. The importance of diastolic BP values is highlighted by their correlation with the metabolic control.

PS3-SAT-457

Severe prenatal renal diseases associated with HNF 1β mutations

L. Madariaga*¹, S. Décramer^6,7, S. Tellier⁶, V. Moriniere^1,2,3, T. Attié³, C. Antignac^1,2,3,4,5, R. Salomon^1,2,4,5, L. Heidet^1,2

¹Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, Paris, France, ²Centre de Référence des Maladies Rénales Héréditaires de l\‘Enfant et de l\’Adulte, Hôpital Necker-Enfants Malades, Paris, France, ³Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France, ⁴INSERM U574, Hôpital Necker-Enfants Malades, Paris, France, ⁵Université Paris Descartes, Paris, France, ⁶Service de Néphrologie Pédiatrique, Hôpital Purpan, Toulouse, France, ⁷Centre de Référence du Sud Ouest des Maladies Rénales Rares, Hôpital Purpan, Toulouse, France

Introduction: Mutations in HNF 1β are associated with various congenital anomalies of the kidney and other organs. The severity of renal disease is extremely variable, even within the same family, and is not correlated with the type of mutation. The aim of this study is to describe the characteristics of 8 foetuses with mutations in HNF 1β and severe renal phenotype that led to termination of pregnancy for medical reasons.

Patients & characteristics: We studied 70 foetuses with severe renal phenotype and found 8 HNF 1β mutations: 4 complete heterozygous deletions and 4 point mutations (c.840delC, c.232G > T, c.827G > A, c.487delG). Parents were tested in 6 cases. Mutations were inherited in 3 cases and de novo in 3 others. Renal anomalies were diagnosed in all foetuses in the second or third trimester by renal ultrasound. The volume of amniotic fluid was variable. Β2-microglobuline was measured in the plasma of 2 foetuses and was elevated in both. Renal ultrasound, foetopathology and kidney histology are described in detail. They always showed renal cysts. Two of them associated incomplete ureteral duplication. Extra-renal anomalies were present in 6 foetuses: genital malformations (septated uterus and bilateral epididymal cysts), pancreas malformations (hypoplasia and partial or complete agenesis), palatine cleft and visceromegaly.

Conclusions: This is the first large cohort of foetuses with severe renal anomalies screened for HNF 1β mutations. Our data show that severe prenatal renal phenotype can be associated with these mutations. We found the mutation in 10% of these foetuses. As already reported, renal phenotype was not correlated with the type or location of the mutation. Due to this phenotypic variability and to the fact that renal prognosis is unpredictable, genetic counselling in these cases is very challenging.

PS3-SAT-458

Managing antenatal hydronephrosis: a ten year experience in a single center

M. Lemac*¹, D. Batinić¹, M. Poropat², D. Milošević¹, Lj. Nižić¹, K. Vrljičak¹

¹Department of Pediatrics, University Hospital Centre Zagreb and Medical School of the University of Zagreb, Croatia, ²Department of Nuclear Medicine and Radiation Protection, University Hospital Centre Zagreb and Medical School of the University of Zagreb, Croatia

Objective: Antenatal hydronephrosis (ANH) is the most common abnormal finding of the urinary tract detected by prenatal ultrasonography. However, the postnatal management of ANH is controversial. Aim of this study was to demonstrate postnatal investigations and treatment of infants with ANH in a single center during a 10 year period.

Methods: We retrospectively analyzed the data of postnatal management of 124 children with ANH. All diagnoses were postnatally confirmed by ultrasonography. Diuretic and static scintigraphy and voiding cystourethorgraphy (VCUG) were performed according to set indications. Therapeutic decisions were made in consensus with urologists.

Results: In the period between 2001 and 2011 we have seen 124 children with ANH (82 boys and 42 girls). The hydronephrosis was found to be bilateral in 45 children, and 79 children had unilateral hydronephrosis, which connotes 169 abnormal renal units (RU). We detected 47 (27.8%) RU with vesicoureteral reflux, 35 (20.7%) RU with ureteropelvic junction obstruction, 34 (20.1%) RU with non-obstructive hydronephrosis, 25 (14.8%) RU with non-obstructive/non-refluxing megaureter, 13 (7.7%) RU with ureterocele, 8 (4.7%) RU with posterior urethral valves, 5 (2.9%) RU with obstructing megaureter and 2 (1.2%) RU were multicystic dysplastic kidneys. Fifthy-four (31.9%) RU were treated surgically, and the rest were followed-up conservatively.

Conclusions: Prognosis and treatment of ANH is largely dependent on the underlying etiology. Early postnatal elucidation of the cause of dilated collecting system is essential. In our study we found more than one third of postnatally confirmed ANH to be caused by obstructive lesions, followed by VUR. However, only one third of all cases required surgical treatment.

PS3-SAT-464

Nephrozystin-4 is a negative regulator of hippo signaling

S. Habbig*¹,², M. Bartram², R.U. Mueller², R. Schwarz², J. Saegmueller², M. Liebau^1,2, T. Benzing², B. Schermer²

¹Pediatric Nephrology, Department of Pediatrics, University of Cologne, Cologne, Germany, ²Renal Division, Department of Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany

The Hippo pathway has recently emerged as a potent regulator of cell proliferation and organ size. The core components MST and LATS act as a kinase cascade which phosphorylates the downstream targets TAZ and YAP. This results in the cytoplasmatic retention and thereby inactivation of both transcriptional co-activators.

Nephronophthisis is the most common genetic cause for endstage renal disease in children and adolescents. Although 11 different disease causing genes have been identified, only little is known about the function of the related nephronophthisis-proteins.

Here, we report that Nephrozystin-4 (NPHP4) negatively regulates Hippo signalling. NPHP4 directly interacts with the central kinase LATS1 and prevents the inactivation of TAZ. In the presence of NPHP4, TAZ is released from 14-3-3 binding and translocates to the nucleus thereby promoting TAZ/TEAD-dependent pro-proliferative transcriptional activity. Consistent with these data, knockdown of NPHP4 results in reduced transcription of target genes of TAZ. Additionally, diminished cell proliferation in human kidney epithelial cells and several tumour cell lines is observed after depletion of NPHP4.

Our data suggest, that NPHP4 regulates cell proliferation through control of Hippo signalling. This might help to understand the phenotype of nephronophthisis characterized by small-sized kidneys and atrophic tubular epithelium. In tubular epithelial cells, loss of NPHP4 might go along with a lack of sufficient TAZ-dependent proliferative signalling resulting in the degenerative phentotype of nephronophthisis. This idea is supported by the observation that two independently generated TAZ deficient mouse models develop cystic kidneys, a phenotype resembling human nephronophthisis.

PS3-SAT-467

UPK3A and FGF7 mutation analysis in Dutch renal adysplasia patients provides further evidence for the role of UPK3A in congenital anomalies of the kidneys and urinary tract (CAKUT) pathogenesis

A.M. van Eerde*¹, K.Y. Renkema², K. Duran¹, E. van Riel¹, Other Autors^1,2,3, M.R. Lilien⁴, T.P.V.M. de Jong⁵, C.G.F. de Kovel¹, N.V.A.M. Knoers^1,2, J.C. Giltay¹

¹Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands, ²Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, ³Department of Urology, Pediatric Urology Centre, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, ⁴Department of Pediatric Nephrology, University Medical Center Utrecht, Utrecht, The Netherlands, ⁵Pediatric Renal Center, University Medical Center Utrecht and Academic Medical Center Amsterdam, Amsterdam, The Netherlands

Renal adysplasia is part of the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT) that forms a major cause of end-stage renal disease in children. Little is known about the origin of renal dysplasia, though it is anticipated that genetic and environmental factors are involved. There is a role for genes expressed during early nephrogenesis in CAKUT etiology. In this study, two genes, uroplakin 3A (UPK3A) and fibroblast growth factor 7 (FGF7), were screened for variants in a phenotypically diverse cohort of 19 Dutch renal adysplasia patients. Four novel, inherited, UPK3A mutations were identified in 3/19 (16%) patients with unilateral multicystic dysplastic kidney. The mutations - c.356T > C (p.Ile119Thr), c.418G > A (p.Gly140Arg), c.450C > A (p.Gly150Gly) and c.545G > A (p.Trp182X)—were not described before and not observed in 96 control chromosomes. As c.418G > A was detected in a patient with VACTERL association (Vertebral defects, Anal atresia or stenosis, Cardiac defects, Tracheo-Esophageal fistula, Radial defects and Renal anomalies, Limb defects), 25 additional DNA samples of VACTERL cases were screened; no mutations in UPK3A were detected. In FGF7, no likely pathogenic mutations were detected. This is the first time a stop-mutation in UPK3A is reported. All UPK3A mutations published so far were reviewed and in silico analyses are presented. This study revealed novel UPK3A mutations strengthening the position of variants in UPK3A in the etiology of renal adysplasia.

PS3-SAT-468

Genes in the ureter budding pathway: association study on vesico-ureteral reflux patients

A.M. van Eerde*¹, N.V.A.M. Knoers¹,², K.Y. Renkema², Other aAutors^1,3,4,5,6, K.P. Wolffenbuttel⁷, J. van den Hoek⁷, W.F. Feitz⁸, T.P.V.M. de Jong⁹, J.C. Giltay¹, C. Wijmenga^1,10

¹Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands, ²Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, ³Department of Pediatric Urology, VU University Medical Center, Amsterdam, The Netherlands, ⁴Department of Pediatric Nephrology, VU University Medical Center, Amsterdam, The Netherlands, ⁵Department of Human Genetics, VU University Medical Center, Amsterdam, The Netherlands, ⁶Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht, The Netherlands, ⁷Department of Pediatric Urology, Sophia Children\’s Hospital, Erasmus Medical Center, Rotterdam, The Netherlands, ⁸Department of Urology, Pediatric Urology Centre, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, ⁹Pediatric Renal Center, University Medical Center Utrecht and Academic Medical Center, Amsterdam, The Netherlands, ¹⁰Department of Genetics, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands

Background: Vesico-ureteral reflux (VUR) is the retrograde passage of urine from the bladder to the urinary tract and causes 8.5% of end-stage renal disease in children. It is a complex genetic developmental disorder, in which ectopic embryonal ureter budding is implicated in the pathogenesis. VUR is part of the spectrum of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).

Methods: We performed an extensive association study for primary VUR using a two-stage, case-control design, investigating 44 candidate genes in the ureter budding pathway in 409 Dutch VUR patients. The 44 genes were selected from the literature and a set of 567 single nucleotide polymorphisms (SNPs) capturing their genetic variation was genotyped in 207 cases and 554 controls. The 14 SNPs with p < 0.005 were included in a follow-up study in 202 cases and 892 controls. Of the total cohort, ∼50% showed a clear-cut primary VUR phenotype and ∼25% had both a duplex collecting system and VUR.

Results: None of the SNPs reached a significant p-value. Common genetic variants in four genes (GREM1, EYA1, ROBO2 and UPK3A) show a trend towards association with the development of primary VUR (GREM1, EYA1, ROBO2) or duplex collecting system (EYA1 and UPK3A). SNPs in three genes (TGFB1, GNB3 and VEGFA) have been shown to be associated with VUR in other populations. Only the result of rs1800469 in TGFB1 hinted at association in our study.

Conclusion: This is the first extensive study of common variants in the genes of the ureter budding pathway and the genetic susceptibility for primary VUR. Even larger cohorts are necessary in order to unravel the true impact of the detected genetic variants.

PS3-SAT-469

Prevalence of underweight and overweight in European pediatric patients on renal replacement therapy

M. Bonthuis* ¹, K. J. van Stralen¹, E. Verrina², A. Edefonti³, K. van Hoeck⁴, A. Peco-Antic⁵, N. Printza⁶, L. Rees⁷, K. J. Jager¹, F. Schaefer⁸

¹ESPN/ERA-EDTA Registry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, ²Gaslini Children’s Hospital, Genoa, Italy, ³Maggiore Policlinico Hospital, Milan, Italy, ⁴Department of Pediatric Nephrology, University Hospital Antwerp, Edegem, Belgium, ⁵University Children’s Hospital, Belgrade, Serbia, ⁶Department of Pediatrics, Aristotle University, HippoKration Hospital, Thessaloniki, Greece, ⁷Department of Nephrology, Gt Ormond Street Hospital for Children NHS Trust, London, United Kingdom, ⁸Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Germany;

Objectives and study: The prevalence of childhood overweight is rising worldwide. While in children on renal replacement therapy (RRT) inadequate nutrition used to be of primary concern, increasing numbers of overweight pediatric RRT patients have recently been reported. Our aim was to study the prevalence of underweight and overweight in the European pediatric RRT population.

Methods: Data on height and weight were collected on all children aged 2 to 17 years who started RRT between 1995 and 2010 in 21 countries within the framework of the ESPN/ERA-EDTA Registry (N = 4482). Body Mass Index (BMI) for height-age was compared to the International Obesity Task Force (IOTF) cut-offs to calculate the prevalence of under- and overweight. IOTF values are based on centile curves at age 18 years passing through adult cut-off points of underweight and overweight from a large international sample. Prevalence estimates were stratified by treatment modality.

Results: Prevalence of under- and overweight was 5.4% and 18.8% in haemodialysis patients, 5.3% and 22% in peritoneal dialysis patients, and was significantly different in transplant patients (1.3% and 42.7% respectively; P < 0.05). For all treatment modalities, pre-school children (N = 422) were significantly less overweight compared to older children (P < 0.05), whereas the prevalence of underweight was higher among pre-school children (N = 4060) (P < 0.05). We did not find a gender difference or a higher prevalence of overweight among children from Southern and Central European countries, as has been reported in the general population.

Conclusion: As in the general European population, overweight is also a problem in children on RRT, especially in school-aged and adolescent patients and transplanted children. The prevalence of underweight is much lower. Nutritional therapy in children on RRT should not only focus on preventing inadequate nutrition but, equally important, on preventing overweight.

PS3-SAT-470

Hypertension in children and adolescents: single centre cross-section patient population

M. Ćuk* ¹, B. Valent-Morić¹, I. Trutin², T. Žigman¹, I. Palčić¹

¹Division of Pediatric Nephrology, Depertment of Pediatrics, University Hospital Center “Sisters of Charity”, Zagreb, Croatia, ²Department of Pediatrics, General Hospital Zabok, Zabok, Croatia

Objective: Hypertension is growing health problem in children and adolescents. There are several epidemiologic studies describing hypertensive population in childhood and adolescents. A cross-section of our patient population was presented.

Methods: Ambulatory Blood Pressure Monitoring (ABPM) hypertension staging was used, (Urbina et al, Hypertension. 2008;52:433). After elevated blood pressure was in primary care office, on at least three occasions, ABPM was performed. Patients with white coat hypertension were excluded. We investigated sex; how many patients were overweighed, had renal disease, were born prematurely and their current hypertension treatment.

Results: There were 142 patients with diagnosed hypertension. The median age at the time of presentation was 14.4 years (y) /4–19 y/. There were 102 (71%) males and 40 (28%) females. Eighty two (57%) patients were overweighed, 11 (15%) had renal disease (multycystic kidney, chronic pyelonephritis, hypoplastic kidney, reflux nephropathy) and 11 (8%) were born as premature newborns. Forty three (29%) were without above mentioned comorbidity. According to the European Guidelines for treating hypertension in children and adolescents (Lurbe E et al, J Hypertens. 2009; 27:1719–1742), in 69 (48,5%) patients the pharmacological treatment was required: in 32 (46%) patients the ACE inhibitor (ACEi) was used, in 14 (21%) Ca-channel blocker, in 14 (21%) ACEi and thiazide diuretic, in 5 (7%) ACEi and Ca-channel blocker combination and in 4 (<1%) other medications were used. Therapy was modified at follow-ups according to the home blood pressure measurements and ABPM in 60 (88%) patients.

Conclusion: Our data show large proportion of overweighed patients and patients born prematurely among hypertensive patients. These children as well as children with renal disease should be targeted population for regular blood pressure monitoring during childhood and adolescence. There is also large proportion of patients that required pharmacological treatment.

PS3-SAT-471

Potential applications of three-dimensional ultrasound imaging of the urinary tract in children

A. Georgieva¹, M. Lilova* ², N. Tsonev¹, P. Marshavelova¹

¹Department of Pediatrics, MHAT Plovdiv, Plovdiv, Bulgaria, ²Department of Pediatrics, Tokuda Hospital, Sofia, Bulgaria

Objectives: Three-dimensional ultrasound (3DUS) imaging entered into medicine over the last fifteen years: initially, on experimental models and for volume measurement in human cadaver organs, later for estimating organ morphology and pathology in clinical and research settings. At present 3DUS imaging is fundamental in obstetrics and gynecology but there are only single reports for the potential applications of 3DUS imaging in the urinary tract in children. The aim of this study is to describe our experience in using 3DUS for imaging of the various urinary tract conditions /UTC/ in children.

Methods: The study enrolled 55 children (25 boys and 30 girls), aged 0 to18 yrs, divided into 2 groups: Group A—25 healthy children, and Group B—30 patients suffering from various UTC. We used two different 3DUS techniques. The potential of 3DUS was discussed on the basis of comparison with conventional 2DUS or other imaging methods, if clinically indicated.

Results: 23/25 healthy children had normal urinary tract; one had renal cyst and the other one—slightly dilated collecting system. 15/30 children with various UTC had hydronephrotic kidneys; 7/30 had renal parenchymal diseases; 5/30—renal cystic changes; 3/30—urinary bladder diseases.

Conclusions: The anatomy of the normal urinary tract and in pathological conditions can be nicely demonstrated on the 3DUS. 3DUS gives an excellent information about anatomy and exact location of parenchymal renal changes. The urinary bladder shape and volume is also achievable. According to our experience 3DUS is accurate diagnostic method: no essential diagnosis was missed. 3DUS is a reliable and precise imaging diagnostic method for evaluating the urinary tract in children.

PS3-SAT-477

Herpes simplex virus hemorrhagic cystitis: case report

A. Georgieva¹, M. Lilova* ², P. Marshavelova¹, N. Tsonev¹

¹Department of Pediatrics, MHAT Plovdiv, Plovdiv, Bulgaria, ²Department of Pediatrics, Tokuda Hospital, Sofia, Bulgaria

Objectives: Herpes Simplex Virus (HSV) infection is one of the commonest viral human infections. There are 2 types of HSV infection: HSV-1 and HSV-2. The clinical manifestation varies according to HSV type and the localization of the infection. HSV infection can be primary or endogenously reactivated.

Methods: We observed 3 years old girl with recurring micro- and macroscopic hematuria in a period of two years. She has been diiagnosed as having nephrolithiasis and urinary tract infection. Because of repeated massive gross haematuria (defined as bladder haematuria in origin) additional instrumental and imaging investigation, cytological and serological analysis and direct isolation of viral DNA were undertaken.

Results: Lab results including blood count and biochemistry were normal. QuantiFERON TB—negative.Urinalysis—non-glomerular haematuria and negative urine culture.

Serological analysis: IgG(HSV-1) -16.6 S/CO (normal range 9–11); two months later—23.5 S/CO, IgG(HSV-2)- 1.9 U/ml (normal range 9–11). USI, CT has shown normal kidneys and ureters. Voiding cystography demonstrated filling defect in the bladder. By urethrocystoscopy—bought ureter\’s ostia looked normal without bleeding from the ureters. Highly bullous mucosa on the bladder fundus and along the bladder left flank was established. Histologically hemorrhagic ulcerous inflammation of the bladder mucosa was found. After specific treatment with Acyclovir haematuria dissapared.

Conclusions: In the presented case combintion of factors for hematuria exists. The last episode of hematuria obviously due to HSV-1 infection. The possible etiology of hematuria in previous episodes might be HSV endogenous reactivation. The clinicians should think about the less common etiological predisposing factors or combination of them in children with hematuria.

PS3-SAT-477

Efficacy of bladder biofeedback treatment for resolution of urinary tract infections in patients with dysfunctional voiding

M. Maternik* ¹, K. Krzeminska¹, A. Zurowska¹

¹Department of Paediatric and Adolescent Nephrology and Hypertension, Gdansk, Poland

Objectives and study: Bladder dysfunction is a well known risk factor for recurrent urinary tract infections (UTI). In children with dysfunctional voiding, defined by ICCS Standardisation Terminology as habitual contractions of the urethral sphincter during voiding, incomplete bladder empting plays a major role in the predisposition for infection. Pelvic floor retraining has been proposed as a treatment option for these patients. The aim of the study was to evaluate the efficacy of bladder biofeedback therapy on the resolution of post-void residual and recurrent UTI.

Methods: 63 children (60 girls and 3 boys) aged 5–18 years (mean: 9,8 yrs) with dysfunctional voiding were assessed for the presence of UTI and post-void residual prior to and following biofeedback bladder training. The duration of observation was 12 months (6 months prior and 6 months following treatment). Significant post void residual (volume >15% of bladder capacity) was assessed by uroflowmetry and ultrasound examination. Pelvic floor training was planned as weekly 20 minutes sessions with an urotherapist for a period of 6 weeks. Each session consisted of 32 repetitions of 5s tension and 30s relaxation of pelvic floor.

Results: A total 105 episodes of UTI were diagnosed during 6 months prior to biofeedback therapy in 47 of 63 patients with dysfunctional voiding. 85% (39/46) of children with dysfunctional voiding and UTI demonstrated significant post void residual. Following pelvic floor treatment 63% (29/46) of children became UTI free over a 6 month period. Furthermore 50% (19/39) showed resolution of postvoid residual. Recurrent UTI were observed in 12/20 (60%) of children with unresolved significant postvoid residual.

Conclusions: Biofeedback treatment of the bladder is an effective adjunctive therapy for children with dysfunctional voiding and recurrent UTI. Pelvic floor retraining eliminates post void residual, a major risk factor for recurrent UTI.

PS3-SAT-478

Diuretic renal scintigraphy in infants with antenatally diagnosed hydronephrosis

M. Poropat* ¹, D. Batinić², M. Lemac², M. Ciglar¹, D. Dodig¹, S. Težak¹

¹Department of Nuclear Medicine and Radiation Protection, University Hospital Centre Zagreb and Medical School of the University of Zagreb, Zagreb, Croatia, ²Department of Paediatrics University Hospital Centre Zagreb and Medical School of the University of Zagreb, Zagreb, Croatia

Objectives: Postnatal approach toward antenatally diagnosed hydronephrosis (ANH) remains controversial. Current algorithm of diagnostic procedures for postnatally confirmed ANH recommend VCUG as the first procedure. The aim of this study was to assess the place of diuretic renal scintigraphy in diagnostic procedures.

Methods: The findings of diuretic renal scintigraphy (F + 20) and VCUG were analysed in 37 infants with ANH confirmed postnatally by ultrasound. Eleven infants had bilateral and 26 unilateral hydronephrosis, which comprised 48 renal units (RU) for analysis.

Results: In total, morphologically normal kidneys were found in 20 (41.7%) and normal diuretic response in 23 (47.9%) RU. In infants with bilateral hydronephrosis characteristic scintigraphic morphological changes were found in 6 out of 22 (27.3%) RU. The pathological diuretic response was found in 6 RU too (1 with obstruction, and 5 with intermediate response). In infants with unilateral hydronephrosis morphological changes were found in 22 of 26 (84.6%) RU. The pathologic diuretic response was registered in 19 of 26 (73.1%) RU (12 with obstruction, and 7 with intermediate response). Among all infants we found 5 with vesicoureteral reflux, in all cases unilateral. Three of them have morphological changes and one complete afunction. One had pathological (intermediate) diuretic response.

Conclusion: Results of our study points that diuretic renal scintigraphy should be the first diagnostic procedure in postnatally confirmed ANH. It has no contraindications, it is easely perfomed, and the most important it has low radiation exposure. Unilateral hydronephrosis should be considered as more serious condition than bilateral hydronephrosis.

PS3-SAT-482

A patient with syndromic renal malformations and a de novo microdeletion at the chromosome 1q42-44 locus

N. Ristoska-Bojkovska* ¹, K. E. Burgess², V. J. Lozanovski^1,3, A. G. Gharavi², Z. Gucev¹, S. Sanna-Cherchi², V. Tasic¹

¹University Children’s Hospital, Medical School, Skopje, Macedonia, ²Division of Nephrology, Columbia University, New York, USA, ³Universitätsklinik für Allgemein, Viszeral und Transplantationschirurgie, Heidelberg, Germany

There is growing evidence that syndromic and non-syndromic forms of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) can result from genomic submicroscopic structural rearrangements. In this report we describe a pediatric patient affected by CAKUT associated to extra-renal malformations caused by a de novo deletion at the chromosome 1q42-44 locus. A 3 year old boy born after uneventful pregnancy presented with facial dysmorphy (epicanthus, hyperthelorism), epilepsy and psychomotor retardation. There was atresia of the left choana, left inguinoscrotal hernia and agenesis of the left kidney. Kariotype analysis was normal. His brother was healthy. His father had a single cortical cyst in the left kidney and his mother had history of seizures. We next performed a genome-wide, high-resolution analysis for copy number variations (CNVs) using the Illumina 610-Quad array, and identified a heterozygous microdeletion of 4.896 Mb at the chr. 1q42-44 locus. This variant was confirmed by quantitative PCR and was absent in both parents and the brother, indicating a de novo occurrence. This deletion was absent in >15,000 controls. Altogether, these data provide strong support for pathogenicity. Deletions involving the distal long arm of chr. 1 have been reported in patients with mental retardation, dysmorphic features and other developmental anomalies, but CAKUT phenotypes are have not been commonly described.

In conclusion, systematic genome-wide screening for pathogenic CNVs in children with CAKUT who have normal kariotype can rapidly lead to diagnosis, explain the phenotype in the family and direct genetic counseling and prenatal diagnostic strategies.

PS3-SAT-484

The development of interstitial fibrosis after bacterial pyelonephritis in rats

N. Zaicova* ¹, V. David², V. Petrovici¹, I. Orlenco², P. Stratulat¹

¹Institution of Scientific Research, Mother and Child Care, Chisinau, Moldova, ²State Medical University, Chisinau, Moldova

Purpose: To study the development of vesico-ureteric reflux (VUR) and of tubulo-interstitial fibrosis and its progression after induction of pyelonephritis in the rat.

Material and methods: The effect of experimental pyelonephritis was studied in 13 white male rats weighing 240 ± 40 g during a period of 6 months. Pyelonephritis was introduced by instillation of 1 ml of microbial culture of E. coli into the urinary bladder. Acute pyelonephritis developed within 24–36 hours and was treated by cefataxim (25 mg i.m. daily) during 5 days in 6 rats, whereas 3 rats served as controls,4 rats died.A VCUG was done after 1, 3 and 6 months, followed by histologic examination, particularly collagen, by HE, picrofuchsin van Gieson and aniline dark blue Mason.

Results: VUR of grade II was detected in 1 of 2 rats at 3 months and of grade III–IV in 2 of 2 rats at 6 months, but no reflux was detected in 2 rats at 1 month. In spite of antibacterial treatment and absent bacterial infection in the treated animals, the inflammatory interstitial lesions, characterised by secondary tubular and vascular damage, persisted in the experimental rats. Inflammatory infiltration by polymorphonuclear cells of varying degree was seen at the side of reflux. At 6 months the fibrotic changes with collagen formation and interstitial infiltration with leucocytes were still marked in the renal parenchyma. This proves that the remaining postinfectious changes remain active and that parenchymal damage reappears.

Conclusion: Pyelonephritis lead to VUR and to tubulo-interstitial and vascular damage, reflecting persistent post infectious pyelonephritis.

PS3-SAT-485

Hypertensive target organ damage and antihypertensive treatment in children with essential hypertension

N. Marčun Varda* ¹, A. Gregorič¹

¹University Medical Centre Maribor, Department of Paediatrics, Maribor, Slovenia

Objectives and study: Hypertensive target organ damage is detectable in children and adolescents and serves us as a marker of importance of elevated blood pressure and for the assessment of blood pressure control. It should include evaluation of heart, kidneys, great vessels and fundoscopy. Antihypertensive treatment at least in part depends on the presence of this damage. The aim of our study was to evaluate target organ damage and antihypertensive treatment in our children and adolescents with essential hypertension.

Methods: Children and adolescents with essential hypertension, diagnosed in our Nephrology Unit in last year, have been included in the study. Some clinical, laboratory and target organ damage data have been collected in retrospective manner.

Results: There were 52 children and adolescents with mean age of 15 ± 3.2 years included in the study. In 57% of them positive family history of hypertension has been found. 30 (57%) children were found to be overweight. Elevated values of cholesterol were detected in 8 children, triglycerides in 10, LDL-cholesterol in 16, homocysteine in 5, insulin in 4 and lipoprotein(a) in 9 of them. Left ventricular hyperthrophy was diagnosed in 14 (27%) hypertensive children, microalbuminuria in 2 (3.8%), retinal abnormalities in 4 (7,6%) and thickening of carotid intima-media in 13 (25%) of them. In 3 of 9 children elevated values of pulse wave velocity were detected. Antihypertensive treatment was prescribed in 19 (36.5%) children, mostly ACE inhibitors. In 3 children two or more medications were needed for blood pressure control.

Conclusions: In our children target organ abnormalities are quite common, especially left ventricular hyperthrophy and thickening of carotid intima-media. In more than third of them antihypertensive treatment has been initiated.

PS3-SAT-487

Ultrasonographic assessment of bladder wall thickness is a sensitive tool for diagnosis of detrusor overactivity in children with primary nocturnal enuresis

S. Charalambous¹, N. Printza* ², M. Bandouraki³, E. Ioannidis⁴, V. Rombis¹, F. Papachristou²

¹Urological Department, Hippokration Hospital,Thessaloniki, Greece, ²1st Pediatric Departement, Aristotles University, Hippokration Hospital,Thessaloniki, Greece, ³Pediatric Radiology Unit, Hippokration Hospital, Thessaloniki, Greece, ⁴Urological Department, Aristotles University, Thessaloniki, Greece

Objectives and study: We investigated the correlations between ultrasonographic bladder wall thickness (BWTh) and urodynamic (UD) findings, in children with primary nocturnal enuresis (PNE).

Methods: Ultrasound measurements (US) and UD were performed on a total of 100 consecutive children 6–14 years old (mean age 9.1 ± 2.19 years) with PNE. The US Protocol was specially designed for the evaluation of bladder wall thickness (BWTh), at the 50% of bladder capacity of the expected bladder volume for the children’s age. All children underwent UD studies for detailed assessment of any underlying bladder overactivity. The children were divided in 4 groups depending on PNE severity:1st group with mild PNE (0–3 times a week) included 25 children, 2nd group with moderated PNE (3–6 times a week) included 30 children, 3rd group with severe PNE (every night) included 20 children and 4th group included 25 children with PNE and diurnal symptoms. The US bladder parameters were then correlated with the UD findings.

Results: The mean BWTh was 1.28 ± 0.17 mm in the 1st group, 1.7 ± 0.52 mm in the 2nd group, 1.96 ± 0.41 mm in the 3rd group and 2.36 ± 0.41 mm in the 4th group. Detrusor Overactivity (DO) occurred in 3/25 children (12%) in the 1st group, in 8/30 (26%) in the 2nd group, in 12/20 children (60%) in the 3rd group and in 17/25 children (68%) in the 4th group. Comparing the BWTh in the four groups with the UD findings, it was found that BWTh was significantly correlated with DO where the maximum amplitude of DO occurred in 20 children who had PNE with diurnal symptoms (p < 0.05). There was also a clear relationship between increasing thickness, decreasing maximum bladder capacity and PNE episodes frequency.

Conclusions: Ultrasonographic assessment of BWTh could be used as a sensitive screening tool for the diagnosis of DO in children with PNE, therefore avoiding UD in some children.

PS3-SAT-489

Approach to ureteropelvic junction obstruction in children: 23 year’s experience

O. Durmaz* ¹, S. Sander², A. Kiyak¹, B. Aydoğdu²

¹Department of Pediatrics, Division of Pediatric Nephrology, Ministry of Health Bakirkoy Maternity and Children Education Hospital, Istanbul, Turkey, ²Department of Pediatric Surgery, Ministry of Health Bakirkoy Maternity and Children Education Hospital, Istanbul, Turkey

Objective: Is to present our 23 years of experience in 211 patients with ureteropelvic junction (UP-J) obstruction on the basis of clinical data .

Patients and method: Records of 211 patients who have been operated for UP-J obstruction between 1987 and 2010 are analysed retrospectively. Patients were divided into two groups: group 1 consisted of prenatally diagnosed patients (n = 149), and group 2 consisted of postnatally diagnosed patients (n = 62).

Results: There were 144 male and 67 female patients. Obstruction was left sided in 122 patients (57,8%), right sided in 81 (38,2%) and bilateral in 8 (4%) patients. Mean age was 6,2 ± 1.3 years (3 months to 12 years) in symptomatically diagnosed cases. Preoperative mean lenght of followup periods were 8,2 ± 1,2 (1–12 months) months and 5,5 ± 1,1 (1–11 months) months, ultrasonographic A-P renal pelvic diameters were 30,8 ± 4,6 mm and 32,8 ± 3,7 mm, split renal functions in scintigraphy were 38,6% and 34,7% in group 1 and 2 respectively. Postoperative mean pelvic diameters were 11,7 ± 1,5 and 12,1 ± 2,6 mm, The most common complications encountered in the postoperative period were attacks of pyelenephritis which was responded to medical theraphy and recurrent UP-J stenosis which required reoperation. Total complication rates were 8,7% in goup 1 and, 6,4% in group 2. The mean lenght of postoperative followup periods were 39,4 ± 8,5 (3–120 months) months in group 1 and, 39 ± 6,4 (2–110 months) months in group 2. Postoperative followup ceased after last evaluation at 10 years in our clinic.

Conclusion: We think that, in patients with UP-J obstruction (prenatally or symptomatically diagnosed) whose pelvic A-P diameters rises above 30 mm and relative renal functions falls below 40% , or if there is a loss of renal function in consecutive scintigraphic studies , the treatment of choice is surgery instead of medical follow up.

PS3-SAT-490

Sharing the responsibility: joint pediatric nephrological and pediatric surgical approach to the patients with vesicoureteral reflux

O. Durmaz* ¹, S. Sander², A. Kiyak¹, Ü. Güvenc², O. Demirali², G. A. Tireli²

¹Department of Pediatrics, Division of Pediatric Nephrology, Ministry of Health Bakirkoy Maternity and Children Education Hospital, Istanbul, Turkey, ²Department of Pediatric Surgery, Ministry of Health Bakirkoy Maternity and Children Education Hospital, Istanbul, Turkey

AIM: The aim of this study is to reflect the experience in patients with vesico ureteral reflux (VUR) who have been treated by a Pediatric Nephrology (PN)-Pediatric Surgery (PS) team.

Material and methods: In this study the medical and surgical records of 902 patients with VUR that had been discussed in regular weekly PN-PS case meetings and followed-up at least 1 year period were retrospectively reviewed.

Results: Of the 902 (537 female, 365 male) patients; 212 (23%) had right-sided, 258 (29%) had left-sided, and 432 (48%) had bilateral VUR. There were 1334 ureters with reflux; grade I in 69 (5%) grade II in 607 (46%) grade III in 433 (32%) grade IV in 165 (12,5%) and grade V in 60 (4,5%). 780 patients (86%) presented with various urinary symptoms and 122 patients (14%) presented with abnormal antenatal ultrasonography findings. Of the 199 patients with suspected neurogenic vesical dysfunction, urodynamic investigation revealed Instabil detrusor contaction in 135 (68%) and DSD in 2 (1%). The most common neurosurgical abnormality was tethered cord and was detected in 14 patients on MRI patients. In this series 627 patients were followed up medically while 275 patients (30%) underwent surgery. VUR disappeared spontaneously in contralateral ureter in 38 patients with bilateral VUR after ipsilateral surgical intervention. With the addition of these 38 cases to the “primary medical” cases; VUR was disappeared spontaneously in 491 patients (74%) out of 665 cases in 1–7 years. The remaining 174 cases are under medical follow-up for 1–3 years.

Conclusion: The development of Pediatric Nephrology has allowed more standart follow-up and treatment parameters in patients with VUR. We think that absence of loss of any kidney and relatively low surgical intervation rate in our series are the best indicators of the benefits of collaborative appoach to the patient with VUR.

PS3-SAT-492

The effect of mutations NR3C2 in children with primary hypertension

O. D. Kara* ¹, B. Sozeri¹, S. Mir¹, A. Berdeli², N. Dincel¹

¹Ege University Faculty of Medicine Department of Pediatric Nephrology, Izmir, Turkey, ²Ege University Faculty of Medicine Department of Molecular Medicine, Izmir, Turkey

As the prevalence of primer hypertension (PHT) is increasing, the last decade witnessed tremendous progress in the molecular mechanisms of PHT pathogenesis. Emerging evidence supports a shift in our understanding of the role of renal Na mechanisms via aldesteron in this pathogenesis. Recently, we have learned that aldosterone has genomic and non genomic signaling pathways through the mineralocorticoid receptor (MR). The objectives of this study were, to test whether mutations in MR gene could be implicated in primary hypertension and to determine the allelic frequency in MR gene.

Fifty patients (23 male, 27 female) with primary hypertension and 10 healthy children matched for age and gender were studied. The diagnosis of PHT we used the following criteria; an average of 2–3 readings of systolic BP and/or diastolic BP exceeding the 95th percentile for age, gender, and height repeated three times over a 2–3 months and Unable to identify a known secondary cause of PHT. We identified a mutation, I180V, in six patients in a heterozygous state. The I180V mutation is present in the MR N terminal domain in exon 2 and might affect the transactivation function. The allele frequency of I180V was 0.06 and 0.05 in patients and normotensive group respectively. This was statistically significant (p = 0.03). In addition to one single nucleotide polymorphism (−2G/C) was detected in 22 patients with a heterozygous, 11 with homozygote state and in 6 healthy individuals (4 in a heterozygote an 2 in homozygote). Clinically and laboratory features were not found statistical significant in patients with I180V mutation compared to others. I180V allele frequency was high in hypertensive group compared to healthy subjects, suggesting that this mutation has an important role in blood pressure regulation. The functional mechanisms of them and their relevance to the clinical features are unclear. Further accumulation of cases with the I180V and 2G > C alleles and a follow-up survey may clarify the possible role of this mutation in hypertension or other clinical phenotypes.

PS3-SAT-495

Is solitary kidney a condition at risk for hypertension? A follow up study in a pediatric population

P. G. Vercelloni* ¹, G. Marra¹, A. Mastrangelo¹, E. Groppali¹, C. Felice Civitillo¹, A. Edefonti¹

¹Fondazione IRCCS Ca\’Granda Ospedale Maggiore Policlinico, Milan, Italy

Objectives: Clinical study of the assessment of hypertension in a population of children with congenital solitary kidney (SK) followed prospectively for 20 years.

Methods: Patients were selected from a wider population of children with congenital uropathies, such as vescico-ureteral reflux and obstruction of the ureteropelvic junction, according to the following criteria: normal renal morphology with US and renal scan, GFR >90 ml/min/1.73 mq and follow up longer than ten years. A total of 88 patients was divided in two groups, one with SK (42) and the other (46) with patients with both kidneys (BK). Blood pressure was sistematically measured at every visit and ABPM was performed every 4 years or before in case of diagnosis of hypertension.

Results: The rate of hypertension was 16,7% in the SK group and 6,5% in the BK group (p-value 0,034).There was a statistically significant difference in almost all the ABPM indices between the two groups

SK(mean ± SD) BK(mean SD) p-value

24 h DBP 0.16 0.87 -0.24 0.70 0.0178

24 h SBP 0.56 1.19 -0.58 0.76 0.0040

day DBP −0.27 0.79 -0.57 0.72 0.0687 (NS)

day SDP 0.17 1.03 -0.26 0.86 0.0355

night DBP 0.58 0.82 0.13 0.77 0.0096

night SBP 1.03 1.24 0.44 0.84 0.0105

Conclusions: Solitary kidney represents a condition at risk for developing hypertension since childhood, therefore blood pressure monitoring is mandatory in this population.

PS3-SAT-509

Detection of vascular changes earlier than overt cardiovascular events in primary hypertensive children

S. Mir* ¹, B. Sozeri¹, M. Deveci², Y. Ozdemir¹

¹Ege University Faculty of Medicine Department of Pediatric Nephrology, Izmir, Turkey, ²Ege University Faculty of Medicine Department of Pediatric Cardiology, Izmir, Turkey

The primary hypertension (PH) carries potential for future end-organdamage (EOD). Generally; cardiovascular damage develops in parallel to renal damage. Overt morbid cardiovascular events are rare in children with PH. Prior studies suggest that renal involvement and left ventricule mass indeks (LVMI) should be detected in PH. We aimed to determine presence of early cardiovascular involvement in children with primary hypertension. We investigated functional and morphological changes in vascular system. Seventy-five consecutive patients (43 male,32 female) withPH and 35 healthy children were studied.Intima-media thickness of the carotid arteries (cIMT,morphological characteristics) was evaluated by 2-D ultrasonography. Carotid-femoral pulse wave velocity and augmentation indeks (PWV,Aix,functional characteristics) by Vicorder system was investigated. The mean age was12.7 ± 3.54 years. Thirteen patients (17.3%) were pre hypertensive, 39 (52%) were in stage-IHT and 23 (30.7%) were in stage-II HT. Five patients had microalbuminuria.

PWVcf was higher in patients (5.87 ± 0.87 m/s) than in controls (5.29 ± 0.67 m/s,P = 0.02). Aix was higher in patients (9.41 ± 8.54%) than in controls (8.36 ± 3.59%,P = 0.04). cIMT was evaluated significantly higher in study group than controls (0.46 ±0.06 mm vs0.35 ± 0.12 mm, respectively, P = 0,01). LVMI was higher in patients (32.9 ± 11.5 vs 28.8 ± 1.55,p = 0.01). Forty-nine of 38 patients were obese whose average body mass index of 28.4 ± 4.8 while 26/75 were non obese. These parameters were found obviously higher in pre-HTstage of obese group. Also the parameters were found obviously higher in stage I of non obese group than controls except LVMI. Controversy,microalbuminuri values were not statistically significant in among stages of BP per two groups. In PT child the markers of vascular morphological and functional damage are increased. Also additional obesity may aggregate this damage. Even though, in stage I, vascular changes became apparent before left ventricule hypertrophy and microalbuminuria. We suggest to evaluate vascular involvement even if no any sign oftraditional end organ damage or microalbuminuria are absent.

PS3-SAT-512

Evaluation of the value of modified nitrite test in early detection of urinary tract infection

S. Zulic* ¹, H. Tahirovic², G. Imamović³, H. Begić⁴

¹Department of Padiatrics, University Clinical Centre Tuzla, Tuzla, Bosnia and Herzegovina, ²Department for Research and Education, University clinical Centre Tuzla, Tuzla, Bosnia and Herzegovina, ³Department of Internal Medicine, Nephrology and Dialysis, University Clinical Centre Tuzla, Tuzla, Bosnia and Herzegovina, ⁴Department of Padiatrics, University Clinical Centre Tuzla, Tuzla, Bosnia and Herzegovina

Objectives: Research was conducted in order to evaluate the value of modified nitrite test in early detection of urinary tract infection (UTI).

Subjects and methods: The cross-sectional research included 300 examinees aged 0–14 years who were examined due to suspicion of UTI in Department of Pediatrics, Tuzla in the period from August 1st, 2006 to August 1st, 2007. From each patient 1 ml of urine that was taken for a urine culture is separated in each two sterile tubes. For the urine in the first tube the presence of nitrite was determined using the test strip. In the case of the negative result second urine tube was added with one drop of sterile 1% NaNO3 solution, and then the urine was left in a thermostat at 37°C for 4 hours, after that the presence of nitrite was tested using test strips. The obtained results were compared with findings of urine culture (1).

Results: Nitrite test has very high specificity (98%), positive predictive value (91%) and positive likelihood ratio (31,7), but lower sensitivity (57%), negative predictive value (87%) and negative likelihood ratio (0,4), so the positive finding is reliable enough to detect UTI, but the negative finding does not exclude its existence. Using the modification of this test according to the aforementioned procedure significantly increased sensitivity (88%), negative predictive value (96%) and negative likelihood value (0,1), so the modified nitrite test is reliable enough to detect UTI and much more reliable then the nitrite to exclude its existence.

Conclusion: Value of the modified nitrite test is characterized by good reliability to detect UTI and it is much more reliable than the nitrite test to exclude its existance. Therefore, this simple, reliable and cheep test can be very usefull, with one sample of urine culture, in the diagnostics of UTI.

PS3-SAT-514

Retinal nerve fiber layer thickness: is it a predictor of target organ damage in hypertensive children?

Z. Ekinci* ¹, A. Babaoglu², A. Toruk³, O. Altıntas³

¹Kocaeli University School of Medicine, Department of Pediatric Nephrology, Kocaeli, Turkey, ²Kocaeli University School of Medicine, Department of Pediatric Cardiology, Kocaeli, Turkey, ³Kocaeli University School of Medicine, Department of Ophtalmology, Kocaeli, Turkey, ⁴Kocaeli University School of Medicine, Department of Ophtalmology, Kocaeli, Turkey

Objectives: The optical coherence tomography (OCT) is a noninvasive optical imaging technique which is the optical analogue of ultrasound imaging. It provides high-resolution cross-sectional images of the retinal nerve fiber layer thickness (RNFLT) that can be qualitatively and quantitatively evaluated. The aim of this cross-sectional study is to evaluate with OCT-3 whether RNFLT has a value as a predictor of target organ damage in hypertensive children.

Patients and methods: Thirty two children (12.45 ± 2.95 years; 15F/17M) with hypertension (6 primary, 26 renal parenchymal hypertension) were enrolled in the study. Echocardiography, 24-hour ambulatory blood pressure monitoring (ABPM) and OCT-3 were performed. Twenty six age and sex matched healthy children were served as controls. Left ventricular hypertrophy was defined as a left ventricular mass index (LVMI) ≥38.6 g/ m2.7.

Results: The patient group showed statistically significant correlations between LVMI and day time and night time systolic blood pressure (SBP) loads and day time and night time indexed SBP, demonstrating the target organ damage caused by hypertension. The average RNFLT of the patient group was 103.19 ± 16.03 μm, whereas 99.50 ± 8.40 μm in the control group, which was not show any significant difference. No significant correlation was recorded between day time and night time SBP loads, day time and night time indexed SBP, dipping and RNFLT on four quadrants (temporal, inferior, nasal, superior). Other parameters of OCT-3, macular values and optic nerve head topography values were also did not show any significant difference from the control group and any correlation was not recorded with ABPM parameters.

Conclusion: The RNFLT in hypertensive children which was measured by OCT-3 was found to be not significantly different from that of normal children. In conclusion RNFLT could not be recorded as a target of hypertension in children.

PS3-SAT-515

In infants with hyponatremia and hyperkalemia, urinalysis should always be performed first!

Z. Ekinci* ¹, K. Kurt²

¹Kocaeli University School of Medicine, Department of Pediatric Nephrology, Kocaeli, Turkey, ²Kocaeli University School of Medicine, Department of Pediatrics, Kocaeli, Turkey

Objectives: Transient pseudohypoaldosteronism (TPHA) has been observed in infants less than 7 months of age suffering from urinary tract malformations, mostly with accompanying urinary tract infections. It was first documented in 1983 by Rodriguez-Soriano et al. It is characterized by salt wasting, hyperkalemia and metabolic acidosis in the presence of significantly elevated plasma renin activity and aldosterone concentrations.

Case report: A 3-month-old girl was admitted to our hospital with vomiting and failure to thrive beginning from the first month of life. She was referred to our clinic as congenital adrenal hyperplasia because of hyperkalemia and hyponatremia. Mild dehydration and malnutrition was present. Laboratory data revealed severe hyponatremia (115 meq/l) hyperkalemia (7 meq/l) and metabolic acidosis (pH: 7.3, HCO3: 17 meq/l). Urine microscopy revealed 40–50 leucocytes/hpf and urine culture was positive for E. coli. Bilateral grade 2 hydronephrosis was detected on urinary tract ultrasonography. Based upon these examinations, diagnosis of TPHA was made and confirmed by elevated plasma aldosterone levels (>500 pg/ml). The infant responded promptly to fluid-electrolyte replacement and antibiotics. Voiding cystourethrography showed bilateral grade IV vesicouretheral reflux. After cessation of fluid and electrolyte therapy, control serum aldosterone level was 145 pg/ml. She was discharged with prophylactic antibiotics, without any sodium supplementation.

Conclusion: As a conclusion, in any child presenting with salt wasting or hyperkalemia, urinary ultrasonography, urinalysis and urine culture should firstly be performed in order to exclude structural renal lesions and/or infection.

PS3-SAT-516

Urinary interleukin-6 and 8: are they useful in distinguishing urinary tract infection in children with neurogenic bladder?

Z. Ekinci* ¹, H. Mutlu²

¹Kocaeli University School of Medicine, Department of Pediatric Nephrology, Kocaeli, Turkey. ²Kocaeli University School of Medicine, Department of Pediatrics, Kocaeli, Turkey

Objectives: Urinary interleukin-6 and 8 (UIL-6, UIL-8) has been reported as a marker of febrile urinary tract infection (UTI) in children. Pyuria and bacteriuria is an expected result of clean intermittent catheterization (CIC) in children with neurogenic bladder. UTI is diagnosed when urine culture is positive with fever, abdominal pain, change in continence pattern, or chance in color or odor of urine in these children. The aim of this cross sectional study is to evaluate whether UIL-6 and UIL-8 levels support the aforementioned clinical rules in the diagnosis of UTI in children with neurogenic bladder.

Patients and methods: The patients were grouped according to the clinical findings and urinalysis. Group 1 (n = 27) comprised of asymptomatic children with normal urinalysis. Group 2 (n = 27) comprised of asymptomatic children with positive nitrite and leucocytes on urinalysis and group 3 (n = 27) symptomatic children with positive nitrite and leucocytes on urinalysis.UIL-6 and UIL-8 were determined by enzyme linked immunosorbent assay.

Results: A total of 71 (F/M: 48/23) patients with neurogenic bladder caused by myelomeningocele with the mean age of 7.08 ± 4.29 (1–18) years were included. All of them were on CIC and anticolinergic drugs. Median UIL-6 concentrations of group 1, 2 and 3 were 1.07 pg/ml (range 0.02–15.08), 1.63 pg/ml (0.04–28.74), 3.41 pg/ml (0.03–44.57) respectively. Median UIL-8 concentrations of group 1, 2 and 3 were 151.70 pg/ml (19.12–3982.23), 382.20 pg/ml (13.06–1929.80), 1098.34 pg/ml (83.13–3609.90) respectively (p = 0.000).

Conclusion: It is concluded that UIL-8 is a significant marker of UTI in children with neurogenic bladder. Disappointingly UIL-6 could not be recorded as a significant marker in these children although previously reported as a marker of acute pyelonephritis in children.

PS3-SAT-517

Serum interleukin-6 and 8: are they useful in distinguishing urinary tract infection in children with neurogenic bladder?

Z. Ekinci* ¹, H. Mutlu²

¹Kocaeli University School of Medicine, Department of Pediatric Nephrology, Kocaeli, Turkey, ²Kocaeli University School of Medicine, Department of Pediatrics, Kocaeli, Turkey

Objectives: Serum interleukin-6 and 8 (SIL-6, SIL-8) has been reported as markers of febrile urinary tract infection (UTI) in children. UTI is diagnosed when urine culture is positive with fever, abdominal pain, change in continence pattern, or chance in color or odor of urine in children with neurogenic bladder. The aim of this cross sectional study is to evaluate whether SIL-6 and SIL-8 levels support the aforementioned clinical rules in the diagnosis of UTI in children with neurogenic bladder.

Methods: The patients were grouped according to the clinical findings and urinalysis. Group 1 (n = 27) comprised of asymptomatic children with normal urinalysis. Group 2 (n = 27) comprised of asymptomatic children with positive nitrite and leucocytes on urinalysis and group 3 (n = 27) symptomatic children with positive nitrite and leucocytes on urinalysis. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), SIL-6 and SIL-8 were determined in all the patients.

Results: A total of 71 (F/M: 48/23) patients with neurogenic bladder caused by myelomeningocele with the mean age of 7.08 ± 4.29 (1–18) years were included. All of them were on CIC and anticolinergic drugs. Median SIL-6 concentrations of group 1, 2 and 3 were 1.10 pg/ml (range 0.10–7.85), 1.06 pg/ml (0.03–13.74), 4.39 pg/ml (0.08–91.01) respectively (p = 0.005). Median SIL-8 concentrations of group 1, 2 and 3 were 20.34 pg/ml (17.71–54.58), 14.03 pg/ml (10.29–239.91), 19.50 pg/ml (10.75–31.09) respectively. SIL-6 were significantly high as ESR (p = 0.005) and CRP (p = 0.000) in children with UTI.

Conclusion: It is concluded that SIL-8 is not a significant marker of UTI in children with neurogenic bladder. However SIL-6 could be useful as ESR and CRP as a significant marker of inflammation in children with neurogenic bladder for the diagnosis of UTI.

PS3-SAT-522

Screening and enrolling children with vesicoureteral reflux: preliminary data from the RIVUR trial

T. Mattoo* ¹, M. Carpenter², R. Chesney³, S. Greenfield⁴, A. Hoberman⁵, R. Keren⁶, R. Mathews⁷, M. Moxey-Mims⁸

¹Children’s Hospital of Michigan, Michigan, USA, ²University of North Carolina, North Carolina, USA, ³University of Tennessee, Tennessee, USA, ⁴Women and Children’s Hospital of Buffalo, New York, USA, ⁵Children’s Hospital of Pittsburgh, Pennsylvania, USA, ⁶Children’s Hospital of Philidelphia, Pennsylvania, USA, ⁷John’s Hopkin’s School of Medicine, Maryland, USA, ⁸National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA

RIVUR is a double-blind placebo-controlled trial of TMP/SMZ prophylaxis in children <6 years old with grade I–IV vesicoureteral reflux (VUR) diagnosed after a maximum of two urinary tract infections. Patient enrollment, which started in June 2007, is going on at 19 sites in the U.S. Through March 1 2011, 573 patients have been randomized in the study. The projected patient recruitment by May 31, 2011 is 609 (101.5%. Since November 2007, 9818 patients have been screened for the study, of which 442 (4.5%) have been randomized; 131 additional enrolled patients are not represented on screening logs due to incomplete screening data collection. The primary referral sources for patient enrollment are urology (2959), radiology (2389), primary care practices (2182), emergency departments (625), laboratories (521) and inpatient (490). Of the 9818 patients, only 1187 (12%) were eligible for randomization, 742 (63%) of whom did not consent for the study participation. Of the total number of 8506 ineligible patients, the most frequent reasons for their ineligibility were failure to meet urinary tract infection criteria in 4356 (51%), no VUR in 3057 (36%), and VCUG result not available in 2376 (28%) patients. In conclusion, the preliminary data from the patients screened so far revealed that an average of 22 children have been screened for each patient recruited, which highlights the challenges faced in patient recruitment for the RIVUR trial or similarly designed randomized controlled studies.

PS3-SAT-523

Possible role of extracellular Zn-containing proteases in renal tissue fibrosis

S. Paunova* ¹, Y. Leontieva¹, A. Kucherenko², L. Revenkova¹, O. Anokhina¹, N. Goltsova³

¹Department of nephrology, Russian state medical university, Moscow, Russian Federation, ²Department of pathophysiology, RAMS Research Institute of Paediatrics, Moscow, Russian Federation, ³Morozov children\’s hospital, Moscow, Russian Federation

Matrix metalloproteinases-2 and −9 (MMP-2,-9) and their tissue inhibitor-1 (TIMP-1) are considered to be important modulators of renal tissue fibrosis.

In order to reveal the role of MMP-2,-9 and TIMP-1 in renal tissue inflammation and subsequent fibrosis 65 children (aged 3–15 years) with UTI were examined. 37 patients with acute presentation (1-st gr.) were examined twice (at onset and after 10–14 days of antibacterial treatment). 28 children (2-nd gr.) had a remission of UTI. 19 healthy children were used as controls. ELISA-measured MMP-2, MMP-9, TIMP-1 in first morning urine standardized to urinary creatinine concentration were evaluated.

Results: All children with UTI demonstrated significant increase of MMP-2, -9 and TIMP-1 in the urine in comparison with controls (p < 0,05). Patients with acute onset of UTI had significantly elevated metalloproteinases and TIMP-1 excretion than children with remission of UTI (p < 0,05). Remarkable, that 5 out of 1-st gr. showed extremely low MMP-2 urine concentration. All of them presented with severe toxic and abdominal syndrome. After treatment MMP-2, -9 and TIMP-1 mostly moved down except 5 children with severe UTI. They elevated MMP-2 level in 3 times, decreasing slightly MMP-9 and TIMP-1.

Conclusion: Elevated level of MMP-2, MMP-9, TIMP-1 in children with remission of UTI may be a result of progressing macrophages infiltration of renal tissue, leading to fibrosis. Significant disturbances in extracellular proteases system in patients with severe UTI may reflect early renal damage mostly due to inflammation or undetected urodynamics disorders, thus these patients should be followed up as a risk group of renal fibrosis.

PS3-SAR-527

Townes brocks syndrome-report of a novel SALL1 mutation in a family with mild clinical presentation

V. Tasic* ¹, A. Kaev², M. Gligorova³, N. Ristoska-Bojkovska¹, V. Lozanovski⁴, Z. Gucev¹, P. Saisawat⁵

¹University Children’s Hospital, Medical School, Skopje, Macedonia, ²Department of Surgery, Medical School Skopje, Macedonia, ³PZU Pedijatrija-Bambi, Strumica, Macedonia, ⁴Universitätsklinik für Allgemein, Viszeral und Transplantationschirurgie, Heidelberg, Germany, ⁵Department of Pediatrics, University of Michigan, Ann Arbor, USA

Townes Brocks syndrome (TBS) is an autosomal dominant multimalformative disorder most commonly affecting ears, thumbs, anus, urogenital tract and heart. Herein we present the first family from Macedonia with TBS and mild clinical presentation.

The index patient is a 3 year old girl with acute pyelonephritis who was diagnosed to have vesicoureteral reflux (VUR) in the right side double system. She underwent STING procedure which led to resolution of her VUR. At the age of 7 during regular checkup she was noticed to have short and broad thumbs and toes. Her mother and brother also had short thumbs. The uncle was deaf and his son had severe congenital heart anomaly. Therefore clinical suspicion for severe TBS in this family was raised. Mutational analysis of the SALL1 gene revealed a novel mutation in the exon 2 (A235T) in the index patient, mother and brother but not in the uncle. Except discrete abnormality of the thumbs, no other malformations were detected in the mother and brother.

In Conclusion-we present a Macedonian family with novel SALL1 mutation and very mild clinical presentation of TBS. Besides VUR in the double system, discrete anomaly of the thumbs and toes was the only clinical feature in this family.

PS3-SAT-529

Urotensin-II levels in children with reflux nephropathy

Z. Gündüz* ¹, D. Babuş Taş², M. Kula³, M. H. Poyrazoğlu¹, S. Tülpar¹, F. Baştuğ¹, S. Yel¹, İ. Dursun¹, R. Düşünsel¹

¹Erciyes University Medical Faculty, Department of Pediatric Nephrology, Kayseri, Turkey, ²Iğdır State Hospital, Kayseri, Turkey, ³Erciyes University Medical Faculty, Department of Nuclear Medicine, Kayseri, Turkey

Objective: Pathogenesis of renal parenchymal injury due to vesicoureteral reflux (VUR) remains controversial. In the present study, it was aimed to evaluate the relationship between renal scarring due to VUR and Urotensin-II (U-II) levels in children.

Patients and methods: 39 children with primary VUR and age and sex matched 24 children without VUR and renal scarring; but, undergoing VUR evaluation who referred to Pediatric Nephrology Outpatient Clinic of Erciyes University recruited to present study. BUN, creatinine, serum and urine U-II levels, urine protein and urine creatinine levels were measured and urine test and urinary culture were performed in each patient. Extend of renal scarring were determined by Dimercaptosuccinic acid (DMSA) and Tc99m-mercaptoacetyltriglisin (MAG3) scintigraphy, while total and individual glomerular filtration rate (GFR) of each kidney were determined by Tc99m Diethylenetriamine penta acetic acid (DTPA) scintigraphy.

Results: There were 28 girls and 11 boys in patient group, whereas 18 girls and 6 boys in control group. No significant difference was found in blood pressures, and serum and urine U-II levels, fractional U-II excretion in the urine between patient and control group (p > 0.05). GFR value was significantly lower in patients with renal scarring (p < 0.05). It was found that urine U-II level, and fractional U-II excretion in urine were significantly higher in patients with history of recurrent urinary tract infection and active urinary tract infection than those without urinary tract infection (p < 0.05). There were an inverse relation between fractional U-II excretion and serum U-II level, a direct relation between urinary U-II and protein excretion rates (p < 0.05).

Conclusion: It was concluded that high urinary U-II excretion was a consequence of proteinuria in children with renal scarring, and that high urinary U-II levels during urinary infection might be related with inflammation and/or transient tubular dysfunction.

PS3-SAT-533

KIM-1 and NGAL: new markers of obstructive nephropathy

K. Taranta–Janusz* ¹, A. Wasilewska¹, W. Dębek¹, W. Zoch–Zwierz¹, E. Kuroczycka–Saniutycz¹, M. Waszkiewicz–Stojda¹

¹Department of Paediatrics and Nephrology, Medical University of Bialystok, Poland

Objectives: Congenital obstructive nephropathy is the primary cause of chronic renal failure in children. Rapid diagnosis and initiation of the treatment are vital to preserve function and/ or to slow down renal injury.

We aimed to check whether uKIM-1 and uNGAL may be useful non-invasive biomarkers in children with congenital hydronephrosis (HN) caused by ureteropelvic junction obstruction (UPJO).

Patients and methods: The study group consisted of 20 children with severe HN, requiring surgery (median aged 2.16 yrs), and 2 control groups (20 patients with mild, non-obstructive HN—control 1, and 25 healthy children—control 2). All examined children had normal renal function. Immunoenzymatic ELISA commercial kits were used to measure KIM-1 and NGAL urinary concentrations.

Results: Preoperative median uKIM-1/ cr. levels were significantly greater than in both control groups. The median uNGAL level was significantly higher in severe HN patients, when compared to control 1 and 2. Three months after surgery urine NGAL decreased significantly (p < 0.05), but was still higher than in control 2 (p < 0.05). ROC analyses have shown a good diagnostic profile for uKIM-1 and uNGAL in identifying differential renal function < 40% in HN patients (AUC—0.8, 0.814, respectively) and < 45% in all examined children (AUC—0.779, 0.868, respectively).

Conclusion: Urinary KIM-1 and NGAL levels are associated with worsening obstruction. Further studies are required to confirm a potential application of uKIM-1 and uNGAL as useful biomarkers for the diagnosis and progression of chronic kidney disease.

PS3-SAT-701

Impact of recombinant human erythropoietin treatment on left ventricular mass and cardiac function in patients with end stage renal disease on haemodialysis

M. A. B. Zahrane* ¹, S. Emam¹, N.A. Rahman¹

¹Pediatric, Aboul Rich Hospital, Cairo University, Cairo, Egypt

Objectives: Objectives of this work was to demonstrate the effect of rHu EPO therapy on LVH and LV systolic function in patients with end stage kidney disease.

Methods: Thirty two patients were enrolled in this study, 14 females and 18 males. Their age ranged from 5 to 17 years along with 15 age and sex matched healthy subjects as controls. The inclusion criteria were; the presence of renal anemia , adequate serum iron status with serum ferritin level of 100 ng/ml or more and a transferrin saturation of >20%, normotension or controlled hypertension and no history of valid heart disease or other systemic illness. We analyzed the laboratory and echocardiographic data before starting EPO treatment and after treatment in period of follow up ranged between 4 and 9 months with a mean of 5.8+/−1.5 months.

Results: Hb level increased from 8.5+/−1.87 to 9.3+/−1.7 gm/dl, Hct level increased from 25.78+/−6.59% to 28.88+/−5.5%, LVMI showd reduction from 108.8+/−41.97 to 97.13+/−43.9 g/m2 , SV decreased from 59.58+/−21.17 to 53.9+/−18.49 ml and finally CO decreased from 5.74+/−2.2 to 5+/−1.5 L/minute. No significant change was detected regarding the HR, EDV, &ESV. LV systolic function was normal at the start of the work and remained so in the follow up examination.

Conclusions: We concluded that in patients with ESRD on chronic hemodialysis, LVH regression can be obtained after partial correction of anemia with rHu EPO which can be also associated with reduction of the high CO encountered in these cases. Weather this regression would improve outcome in haemodialysis patients remain to be established.