Abstract
Background
Glomerular podocyte molecules are involved in the pathogenesis of congenital nephrotic syndrome. However, their role in primary nephrotic syndrome is not clear. This study investigated the expression of nephrin, podocin and synaptopodin in primary nephrotic syndrome.
Methods
Eighty-seven patients with primary nephrotic syndrome including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and membranoproliferative glomerulonephritis Type I (MPGN) were included in the study. Glomerular expression of nephrin, podocin and synaptopodin was studied in renal biopsies by immunofluorescence and immunohistochemistry. Correlation of expression with clinical and biochemical parameters was performed.
Results
The pattern of expression for all podocyte proteins in controls was uniform fine granular along the capillary walls towards the visceral epithelial cell aspect. Glomerular expression of nephrin was present in all renal biopsies and was similar to that in controls. Glomerular synaptopodin expression was seen in all MN and MPGN patients, while it was seen in 74 % (17/23) MCD and 93.5 % (29/31) FSGS. Reduced synaptopodin expression showed no correlation with clinical and biochemical factors. Podocin expression was present in 5/23 MCD (22 %), 3/31 FSGS (9.6 %), 13/17 MN (76.4 %) and 13/16 MPGN (81 %) patients. The reduced expression of podocin significantly correlated with the degree of proteinuria (p = 0.032). No correlation with age, gender and serum creatinine level was observed.
Conclusion
Reduction of glomerular podocin expression found in MCD and FSGS is related to the amount of proteinuria. Our findings suggest that alteration in podocyte phenotype may not be a primary event and may reflect the degree of podocyte injury in primary nephrotic syndrome.
Similar content being viewed by others
References
Barisoni L, Mundel P. Podocyte biology and the emerging understanding of podocyte diseases. Am J Nephrol. 2003;23:353–60.
Lenkkeri U, Männikkö M, McCready P, Lamerdin J, Gribouval O, Niaudet PM, Antignac CK, Kashtan CE, Homberg C, Olsen A, Kestilä M, Tryggvason K. Structure of the gene for congenital nephrotic syndrome of the Finnish type (NPHS1) and characterization of mutations. Am J Hum Genet. 1999;64:51–61.
Roselli S, Gribouval O, Boute N, Sich M, Benessy F, Attié T, Gubler MC, Antignac C. Podocin localizes in the kidney to the slit diaphragm area. Am J Pathol. 2002;160:131–9.
Srivastava T, Garola RE, Whiting JM, Alon US. Synaptopodin expression in idiopathic nephrotic syndrome of childhood. Kidney Int. 2001;59:118–25.
Horinouchi I, Nakazato H, Kawano T, Iyama K, Furuse A, Arizono K, Machida J, Sakamoto T, Endo F, Hattori S. In situ evaluation of podocin in normal and glomerular diseases. Kidney Int. 2003;64:2092–9.
Doublier S, Ruotsalainen V, Salvidio G, Lupia E, Biancone L, Conaldi PG, Reponen P, Tryggvason K, Camussi G. Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome. Am J Pathol. 2001;158:1723–31.
Huh W, Kim DJ, Kim MK, Kim YG, Oh HY, Ruotsalainen V, Tryggvason K. Expression of nephrin in acquired human glomerular disease. Nephrol Dial Transplant. 2002;17:478–84.
Kim BK, Hong HK, Kim JH, Lee HS. Differential expression of nephrin in acquired human proteinuric diseases. Am J Kidney Dis. 2002;40:964–73.
Hingorani SR, Finn LS, Kowalewska J, McDonald RA, Eddy AA. Expression of nephrin in acquired forms of nephrotic syndrome in childhood. Pediatr Nephrol. 2004;19:300–5.
Patrakka J, Ruotsalainen V, Ketola I, Holmberg C, Heikinheimo M, Tryggvason K, Jalanko H. Expression of nephrin in pediatric kidney diseases. J Am Soc Nephrol. 2001;12:289–96.
Koop K, Eikmans M, Baelde HJ, Kawachi H, De Heer E, Paul LC, Bruijn JA. Expression of podocyte-associated molecules in acquired human kidney diseases. J Am Soc Nephrol. 2003;14:2063–71.
Barisoni L, Kriz W, Mundel P, D’Agati V. The dysregulated podocyte phenotype: a novel concept in the pathogenesis of collapsing idiopathic focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol. 1999;10:51–61.
Tonna SJ, Needham A, Polu K, Uscinski A, Appel GB, Falk RJ, Katz A, Al-Waheeb S, Kaplan BS, Jerums G, Savige J, Harmon J, Zhang K, Curhan GC, Pollak MR. NPHS2 variation in focal and segmental glomerulosclerosis. BMC Nephrol. 2008;9:13.
He N, Zahirieh A, Mei Y, Lee B, Senthilnathan S, Wong B, Mucha B, Hildebrandt F, Cole DE, Cattran D. Recessive NPHS2 (podocin) mutations are rare in adult-onset idiopathic focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2007;2:31–7.
McKenzie LM, Hendrickson SL, Briggs WA, Dart RA, Korbet SM, Mokrzycki MH, Kimmel PL, Ahuja TS, Berns JS, Simon EE. NPHS2 variation in sporadic focal segmental glomerulosclerosis. J Am Soc Nephrol. 2007;18:2987–95.
Mollet G, Ratelade J, Boyer O, Muda AO, Morisset L, Lavin TA, Kitzis D, Dallman MJ, Bugeon L, Hubner N, Gubler MC, Antignac C, Esquivel EL. Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome. J Am Soc Nephrol. 2009;10:2181–9.
Wang G, Lai FM, Lai KB, Chow KM, Kwan BC, Li KT, Szeto CC. Intra-renal and urinary mRNA expression of podocyte-associated molecules for the estimation of glomerular podocyte loss. Ren Fail. 2010;32:372–9.
Acknowledgments
The study was carried out by the intramural research grant (A-06: PGI/IMP/EC/44/2008) from the author’s institute.
Conflict of interest
All the authors have declared no competing interest.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Agrawal, V., Prasad, N., Jain, M. et al. Reduced podocin expression in minimal change disease and focal segmental glomerulosclerosis is related to the level of proteinuria. Clin Exp Nephrol 17, 811–818 (2013). https://doi.org/10.1007/s10157-013-0775-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10157-013-0775-y