Skip to main content
SpringerLink
Log in

A predictive model of progressive chronic kidney disease in idiopathic nephrotic syndrome

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

There are limited data on the risk factors for chronic kidney disease (CKD) in children with idiopathic nephrotic syndrome (INS). This retrospective cohort study aimed to develop a predictive model for CKD progression in children with INS.

Methods

Between 1970 and 2012, a total of 294 patients with INS were followed up. The primary outcome was progression to CKD stage 3 or higher. A predictive model was developed using a Cox proportional hazards model. A score was calculated using b-coefficients and summing up points assigned to each significant variable. Prognostic score was grouped into categories: low risk, medium risk, and high risk.

Results

Median follow-up was 6.9 years. Median renal survival was 26.1 years and probability of CKD stage 3 or higher was 8 % in 10 years. Multivariate analysis showed that the most accurate model included initial age, hematuria, and steroid resistance. Accuracy was high with a c-statistic of 0.95 (95 % confidence interval [CI] 0.91–0.99), 0.92 (95 % CI 0.88–0.96), and 0.92 (95 % CI 0.87–0.97) at 2, 5, and 10 years of follow-up respectively. By survival analysis, 10-year renal survival was 100 % for the low-risk and 95 % for the medium-risk group, while 40 % of high-risk patients would exhibit CKD stage 3 or higher (P < 0.001).

Conclusions

Our predictive model of CKD may contribute to the early identification of a subgroup of INS patients at a high risk of renal dysfunction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Gipson DS, Massengill SF, Yao L, Nagaraj S, Smoyer WE, Mahan JD, Wigfall D, Miles P, Powell L, Lin JJ, Trachtman H, Greenbaum LA (2009) Management of childhood onset nephrotic syndrome. Pediatrics 124:747–757

    Article  PubMed  Google Scholar 

  2. Fakhouri F, Bocquet N, Taupin P, Presne C, Gagnadoux MF, Landais P, Lesavre P, Chauveau D, Knebelmann B, Broyer M, Grünfeld JP, Niaudet P (2003) Steroid-sensitive nephrotic syndrome: from childhood to adulthood. Am J Kidney Dis 41:550–557

    Article  PubMed  Google Scholar 

  3. Banazsak B, Banaszak P (2012) The increasing incidence of initial steroid resistance in childhood nephrotic syndrome. Pediatr Nephrol 27:927–932

    Article  Google Scholar 

  4. Filler G, Young E, Geier P, Carpenter B, Drukker A, Feber J (2003) Is there really an increase in non-minimal change nephrotic syndrome in children? Am J Kidney Dis 42:1107–1113

    Article  PubMed  Google Scholar 

  5. Bibiloni Mdel M, Pons A, Tur JA (2013) Prevalence of overweight and obesity in adolescents: a systematic review. ISRN Obes 2013:392747

    PubMed  Google Scholar 

  6. Taal MW, Brenner BM (2006) Predicting initiation and progression of chronic kidney disease: developing renal risk scores. Kidney Int 70:1694–1705

    Article  CAS  PubMed  Google Scholar 

  7. Taal MW, Brenner BM (2008) Renal risk scores: progress and prospects. Kidney Int 73:1216–1219

    Article  CAS  PubMed  Google Scholar 

  8. Staples AO, Greenbaum LA, Smith JM, Gipson DS, Filler G, Warady BA, Martz K, Wong CS (2010) Association between clinical risk factors and progression of chronic kidney disease in children. Clin J Am Soc Nephrol 5:2172–2179

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. International Study of Kidney Disease in Children (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr 98:561–564

  10. Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr (1997) Prognostic significance of the early course of minimal change nephrotic syndrome: report of the international study of kidney disease in children. J Am Soc Nephrol 8:769–776

    CAS  PubMed  Google Scholar 

  11. Kidney disease: improving global outcomes (KDIGO) Glomerulonephritis Work Group (2012) KDIGO clinical practice guideline for glomerulonephritis. Kidney Int 2:139–274 http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO-GN-Guideline.pdf

  12. Mendoza AS, Reznik M, Griswold WR, Krensky AM, Yorgin PD, Tune BM (1990) Treatment of steroid-resistant focal segmental glomerulosclerosis with pulse methylprednisolone and alkylating agents. Pediatr Nephrol 4:303–307

    Article  CAS  PubMed  Google Scholar 

  13. IBGE (2000) Censo 2000, Rio de Janeiro, Brazil, Brazilian Institute of Geography and Statistics. http://www.ibge.gov.br/home/estatistica/populacao/censo2000/populacao/censo2000_populacao.pdf

  14. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) Fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576

    Article  Google Scholar 

  15. Dean AG, Dean JA, Coulombier D, Burton AH, Brendel KA, Smith DC, Dicker RC, Sullivan KM, Fagan RF (1996) Epi info, version 6: a word processing, database, and statistics program for epidemiology on microcomputers, Atlanta, Georgia, Centers for Disease Control and Prevention. stacks.cdc.gov/view/cdc/23189/cdc_23189_DS1.pdf

  16. Schwartz GJ, Brion LP, Spitzer A (1987) The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin N Am 34:571–590

    CAS  Google Scholar 

  17. Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637

    Article  PubMed Central  PubMed  Google Scholar 

  18. Ravani P, Parfrey P, Gadag V, Malberti F, Barrett B (2007) Clinical research of kidney diseases III: principles of regression and modelling. Nephrol Dial Transplant 22:3422–3430

    Article  PubMed  Google Scholar 

  19. Cerqueira DC, Soares CM, Silva VR, Magalhães JO, Barcelos IP, Duarte MG, Pinheiro SV, Colosimo EA, Simões e Silva AC, Oliveira EA (2014) A predictive model of progression of CKD to ESRD in a predialysis pediatric interdisciplinary program. Clin J Am Soc Nephrol 9:728–735

  20. Sullivan LM, Massaro JM, D’Agostino RB Sr (2004) Presentation of multivariate data for clinical use: the Framingham study risk score functions. Stat Med 23:1631–1660

    Article  PubMed  Google Scholar 

  21. Moons KG, Kengne AP, Woodward M, Royston P, Vergouwe Y, Altman DG, Grobbee DE (2012) Risk prediction models. I. Development, internal validation, and assessing the incremental value of a new (bio)marker. Heart 98:683–690

    Article  PubMed  Google Scholar 

  22. Moons KG, Kengne AP, Grobbee DE, Royston P, Vergouwe Y, Altman DG, Woodward M (2012) Risk prediction models. II. External validation, model updating, and impact assessment. Heart 98:691–698

    Article  PubMed  Google Scholar 

  23. Harrell FE Jr, Lee KL, Mark DB (1996) Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 15:361–387

    Article  PubMed  Google Scholar 

  24. Cook NR, Buring JE, Ridker PM (2006) The effect of including C-reactive protein in cardiovascular risk prediction models for women. Ann Intern Med 145:21–29

    Article  CAS  PubMed  Google Scholar 

  25. Hosmer DW, Hosmer T, Le Cessie S, Lemeshow S (1997) A comparison of goodness-of-fit tests for the logistic regression model. Stat Med 16:965–980

    Article  CAS  PubMed  Google Scholar 

  26. Steyerberg EW, Vickers AJ, Cook NR, Gerds T, Gonen M, Obuchowski N, Pencina MJ, Kattan MW (2010) Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology 21:128–138

    Article  PubMed Central  PubMed  Google Scholar 

  27. Steyerberg EW, Harrell FE Jr, Borsboom GJ, Eijkemans MJ, Vergouwe Y, Habbema JD (2001) Internal validation of predictive models: efficiency of some procedures for logistic regression analysis. J Clin Epidemiol 54:774–781

    Article  CAS  PubMed  Google Scholar 

  28. International Study of Kidney Disease in Children (1981) Primary nephrotic syndrome in children: clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. A report of the International Study of Kidney Disease in Children. Kidney Int 20:765–771

  29. McKinney PA, Feltbower RG, Brocklebank JT, Fitzpatrick MM (2001) Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire, UK. Pediatr Nephrol 16:1040–1044

    Article  CAS  PubMed  Google Scholar 

  30. Srivastava RN, Mayekar G, Anand R, Choudhry VP, Ghai OP, Tandon HD (1975) Nephrotic syndrome in Indian children. Arch Dis Child 50:626–630

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Sharples PM, Poulton J, White RH (1985) Steroid responsive nephrotic syndrome is more common in Asians. Arch Dis Child 60:1014–1017

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Mekahli D, Liutkus A, Ranchin B, Yu A, Bessenay L, Girardin E, Van Damme-Lombaerts R, Palcoux JB, Cachat F, Lavocat MP, Bourdat-Michel G, Nobili F, Cochat P (2009) Long-term outcome of idiopathic steroid-resistant nephrotic syndrome: a multicenter study. Pediatr Nephrol 24:1525–1532

    Article  PubMed  Google Scholar 

  33. Paik KH, Lee BH, Cho HY, Kang HG, Ha IS, Cheong HI, Jin DK, Moon KC, Choi Y (2007) Primary focal segmental glomerular sclerosis in children: clinical course and prognosis. Pediatr Nephrol 22:389–395

    Article  PubMed  Google Scholar 

  34. El-Refaey AM, Bakr A, Hammad A, Elmougy A, El-Houseeny F, Abdelrahman A, Sarhan A (2010) Primary focal segmental glomerulosclerosis in Egyptian children: a 10-year single centre experience. Pediatr Nephrol 25:1369–1373

    Article  PubMed  Google Scholar 

  35. Southwest Pediatric Nephrology Study Group (1985) Focal segmental glomerulosclerosis in children with idiopathic nephrotic syndrome. A report of the Southwest Pediatric Nephrology Study Group. Kidney Int 27:442–449

    Article  Google Scholar 

  36. International Study of Kidney Disease in Children (1978) Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease in Children. Kidney Int 13:159–165

    Article  Google Scholar 

  37. Abrantes MM, Cardoso LSB, Lima EM, Silva JMP, Diniz JS, Bambirra EA, Oliveira EA (2006) Predictive factors of chronic kidney disease in primary focal segmental glomerulosclerosis. Pediatr Nephrol 21:1003–1012

    Article  PubMed  Google Scholar 

  38. Zagury A, Oliveira AL, Montalvão JAA, Novaes RHL, Moraes CAP, Tavares MS (2013) Síndrome Nefrótica córtico-resistente na criança: evolução e fatores de risco para doença renal crônica terminal. J Bras Nefrol 35:191–199

    Article  PubMed  Google Scholar 

  39. Wuhl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, Zurowska A, Testa S, Jankauskiene A, Emre S, Caldas-Afonso A, Anarat A, Niaudet P, Mir S, Bakkaloglu A, Enke B, Montini G, Wingen AM, Sallay P, Jeck N, Berg U, Caliskan S, Wygoda S, Hohbach-Hohenfellner K, Dusek J, Urasinski T, Arbeiter K, Neuhaus T, Gellermann J, Drozdz D, Fischbach M, Moller K, Wigger M, Peruzzi L, Mehls O, Schaefer F (2009) ESCAPE Trial Group: strict blood pressure control and progression of renal failure in children. N Engl J Med 361:1639–1650

    Article  PubMed  Google Scholar 

  40. Chang JW, Tsai HL, Yang LY, Chen TJ (2012) Epidemiology and predictors of end-stage renal disease in Taiwanese children with idiopathic nephrotic syndrome. J Epidemiol 22:517–522

    Article  PubMed Central  PubMed  Google Scholar 

  41. Szeto CC, Lai FM, Chow KM, Kwan BC, Kwong VW, Leung CB, Li PK (2014) Long-term outcome of biopsy-proven minimal change nephropathy in Chinese adults. Am J Kidney Dis 65:710–718

    Article  PubMed  Google Scholar 

  42. Ruth EM, Kemper MJ, Leumann EP, Laube GF, Neuhas TJ (2005) Children with steroid-sensitive nephrotic syndrome come of age: long-term outcome. J Pediatr 147:202–207

    Article  PubMed  Google Scholar 

  43. Chang JW, Tsai HL, Wang HH, Yang LY (2009) Clinicopathological features and prognosis of Chinese children with idiopathic nephrotic syndrome between different age groups. Eur J Pediatr 168:1189–1194

    Article  PubMed  Google Scholar 

  44. Cattran DC, Panduranga R (1998) Long-term outcome in children and adults with classic focal segmental glomerulosclerosis. Am J Kidney Dis 32:72–79

  45. Chun MJ, Korbet SM, Schwartz MM, Lewis EJ (2004) Focal segmental glomerulosclerosis in nephrotic adults: presentation, prognosis, and response to therapy of the histologic variants. J Am Soc Nephrol 15:2169–2177

    Article  PubMed  Google Scholar 

  46. Vivante A, Calderon-Margalit R, Skorecki K (2013) Hematuria and risk for end-stage kidney disease. Curr Opin Nephrol Hypertens 22:325–330

    Article  CAS  PubMed  Google Scholar 

  47. Chadban SJ, Atkins RC (2005) Glomerulonephritis. Lancet 365:1797–1806

    Article  CAS  PubMed  Google Scholar 

  48. Pereira WF, Brito-Melo GE, Guimarães FT, Carvalho TG, Mateo EC, Simões e Silva AC (2014) The role of the immune system in idiopathic nephrotic syndrome: a review of clinical and experimental studies. Inflamm Res 63:1–12

  49. Soares CM, Diniz JS, Lima EM, Silva JM, Oliveira GR, Canhestro MR, Colosimo EA, Simões e Silva AC, Oliveira EA (2008) Clinical outcome of children with chronic kidney disease in a pre-dialysis interdisciplinary program. Pediatr Nephrol 23:2039–2046

  50. Park M, Yoon E, Lim YH, Kim H, Choi J, Yoon HJ (2014) Renal hyperfiltration as a novel marker of all-cause mortality. J Am Soc Nephrol 26:1426–1433

Download references

Acknowledgments

The authors dedicate this work to the deceased Professor José Silvério Santos Diniz, founder of the Pediatric Nephrology Unit, Clinics Hospital, Federal University of Minas Gerais, Brazil. The authors thank Dr Luiz Sérgio Bahia Cardoso and all other colleagues who processed medical records, managed patients, performed renal biopsies, and assisted with follow-up.

Financial support

FAPEMIG (Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Brazil), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil) ,and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior).

Author information

Authors and Affiliations

  1. Pediatric Nephrology Unit, Federal University of Minas Gerais, Belo Horizonte, Brazil

    Ana Carmen Quaresma Mendonça, Eduardo Araújo Oliveira, Brunna Pinto Fróes, Ana Cristina Simões e Silva & Sérgio Veloso Brant Pinheiro

  2. Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil

    Lauro Damasceno Carvalho Faria, Juliana Silva Pinto, Maira Melo Ibrahim Nogueira, Gabriella Oliveira Lima, Priscila Isa Resende & Natália Silva Assis

Authors
  1. Ana Carmen Quaresma Mendonça
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eduardo Araújo Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brunna Pinto Fróes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lauro Damasceno Carvalho Faria
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juliana Silva Pinto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maira Melo Ibrahim Nogueira
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gabriella Oliveira Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Priscila Isa Resende
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Natália Silva Assis
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ana Cristina Simões e Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sérgio Veloso Brant Pinheiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sérgio Veloso Brant Pinheiro.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mendonça, A.C.Q., Oliveira, E.A., Fróes, B.P. et al. A predictive model of progressive chronic kidney disease in idiopathic nephrotic syndrome. Pediatr Nephrol 30, 2011–2020 (2015). https://doi.org/10.1007/s00467-015-3136-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-015-3136-0

Keywords

Search

Navigation