Abstract
Background
A high prevalence of chronic kidney disease among children with focal segmental glomerulosclerosis (FSGS) leads to a permanent quest for good predictors of kidney dysfunction. Thus, we carried out a retrospective cohort study in order to examine known clinical and morphological predictors of adverse outcome, as well as to investigate glomerular nestin expression as a potential new early predictor of kidney dysfunction in children with FSGS. Relationships between nestin expression and clinical and morphological findings were also investigated.
Methods
Among 649 renal biopsy samples, obtained from two children’s hospitals, FSGS was diagnosed in 60 children. Thirty-eight patients, who met the criteria for this study, were followed up for 9.0 ± 5.2 years. Using Kaplan–Meier and Cox’s regression analysis, potential clinical and morphological predictors were applied in two models of prediction: after disease onset and after the biopsy.
Results
The present study revealed the following significant predictors of kidney dysfunction: patients’ ages at disease onset, as well as age at biopsy, resistance to corticosteroid treatment, serum creatinine level, urine protein/creatinine ratio, vascular involvement, tubular atrophy, interstitial fibrosis, and decreased glomerular nestin expression.
Conclusions
The most important finding of our study is that nestin can be used as a potential new early morphological predictor of kidney dysfunction in childhood onset of FSGS, since nestin has been obviously decreased in both sclerotic and normal glomeruli seen by light microscopy.
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References
D’Agati VD, Kaskel FJ, Falk RJ (2011) Focal segmental glomerulosclerosis. N Engl J Med 365:2398–411
Hogg R, Middleton J, Vehaskari VM (2007) Focal segmental glomerulosclerosis—epidemiology aspects in children and adults. Pediatr Nephrol 22:183–186
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
Gipson DS, Gibson K, Gipson PE, Watkins S, Moxey-Mims M (2007) Therapeutic approach to FSGS in children. Pediatr Nephrol 22:28–36
Reidy K, Kaskel FJ (2007) Pathophysiology of focal segmental glomerulosclerosis. Pediatr Nephrol 22:350–354
Abrantes MM, Cardoso LSB, Lima EM, Penido Silva JM, Diniz JS, Bambirra EA, Oliveira EA (2006) Predictive factors of chronic kidney disease in primary focal segmental glomerulosclerosis. Pediatr Nephrol 21:1003–1012
Gbadegesin R, Lavin P, Foreman J, Winn M (2011) Pathogenesis and therapy of focal segmental glomerulosclerosis: an update. Pediatr Nephrol 26:1001–1015
Ulinski T (2010) Recurrence of focal segmental glomerulosclerosis after kidney transplantation: strategies and outcome. Curr Opin Organ Transplant 15:628–632
ISKDC (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
Shankland SJ (2006) The podocyte’s response to injury: role in proteinuria and glomerulosclerosis. Kidney Int 69:2131–2147
Michalczyk K, Ziman M (2005) Nestin structure and predicted function in cellular cytoskeletal organization. Histol Histopathol 20:665–671
Su W, Chen J, Yang H, You L, Xu L, Wang X, Li R, Gao L, Gu Y, Lin S, Xu H, Breyer MD, Hao CM (2007) Expression of nestin in the podocytes of normal and diseased human kidneys. Am J Physiol Regul Integr Comp Physiol 292:R1761–R1767
Bertelli E, Regoli M, Fonzi L, Occhini R, Mannucci S, Ermini L, Toti P (2007) Nestin expression in adult and developing human kidney. J Histochem Cytochem 55:411–421
Chen J, Boyle S, Zhao M, Su W, Takahashi K, Davis L, Decaestecker M, Takahashi T, Breyer MD, Hao CM (2006) Differential expression of the intermediate filament protein nestin during renal development and its localization in adult podocytes. J Am Soc Nephrol 17:1283–1291
Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263
Hodson EM, Knight F, Willis NS, Craig JC (2007) Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev CD001533
Kemper JM, van Husen M (2011) New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol 26:881–892
Ehrich JH, Brodehl J (1993) Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft für pädiatrische Nephrologie. Eur J Pediatr 152:357–361
Amann K, Haas CS (2006) What you should to know about the work-up of renal biopsy. Nephrol Dial Transplant 21:1157–1161
D’Agati VD, Fogo AB, Bruijn JA, Jennette JC (2004) Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis 43:368–382
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
Jefferson JA, Alpers CE, Shankland SJ (2011) Podocyte biology for the bedside. Am J Kidney Dis 58:835–845
Gheissari A, Taheri D, Mozafarpour S, Beigy H, Samanianpoor P, Merrikhi A, Farajzadegan Z (2012) The expression of cytoskeletal proteins in kidney specimens of children with primary focal segmental glomerulosclerosis. Indian J Nephrol 22:444–450
Wharram BL, Goyal M, Wiggins JE, Sanden SK, Hussain S, Filipiak WE, Saunders TL, Dysko RC, Kohno K, Holzman LB, Wiggins RC (2005) Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J Am Soc Nephrol 16:2941–2952
Korbet SM (1999) Clinical picture and outcome of primary focal segmental glomerulosclerosis. Nephrol Dial Transplant 14:68–73
Martinelli R, Okumura AS, Pereira LJ, Rocha H (2001) Primary focal segmental glomerulosclerosis in children: prognostic factors. Pediatr Nephrol 16:658–661
Hoseini R, Otukesh H, Fereshtehnejad SM, Tahoori A, Hooman N, Rahimzadeh N, Sadr S (2012) Prevalence and outcome of focal segmental glomerulosclerosis in Iranian children with nephrotic syndrome. Iran J Kidney Dis 6:18–24
Gipson DS, Chin H, Presler TP, Jennette C, Ferris ME, Massengill S, Gibson K, Thomas DB (2006) Differential risk of remission and ESRD in childhood FSGS. Pediatr Nephrol 21:344–349
Troyanov S, Wall CA, Miller JA, Scholey JW, Cattran DC (2005) Focal and segmental glomerulosclerosis: definition and relevance of partial remission. J Am Soc Nephrol 16:1061–1068
Abrantes MM, Cardoso LSB, Lima EM, Silva JMP, Diniz JS, Bambirra EA, Oliveira EA (2006) Clinical course of 110 children and adolescents with primary focal segmental glomerulosclerosis. Pediatr Nephrol 21:482–489
Markovic-Lipkovski J, Müller CA, Risler T, Bohle A, Müller GA (1991) Mononuclear leukocytes, expression of HLA class II antigens and intercellular adhesion molecule 1 in focal segmental glomerulosclerosis. Nephron 59:286–293
Gellermann J, Ehrich JHH, Querfeld U (2012) Sequential maintenance therapy with cyclosporin A and mycophenolate mofetil for sustained remission of childhood steroid-resistant nephrotic syndrome. Nephrol Dial Transplant 27:1970–1978
Acknowledgement
This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, project number OI 175047.
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Životić, M., Bogdanović, R., Peco-Antić, A. et al. Glomerular nestin expression: possible predictor of outcome of focal segmental glomerulosclerosis in children. Pediatr Nephrol 30, 79–90 (2015). https://doi.org/10.1007/s00467-014-2893-5
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DOI: https://doi.org/10.1007/s00467-014-2893-5