Skip to main content
SpringerLink
Log in

Expression of nephrin in acquired forms of nephrotic syndrome in childhood

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

Abstract

Nephrin is a podocyte adhesion molecule located at the slit diaphragm between adjacent glomerular epithelial cells. Mutations in the gene encoding nephrin result in the absence of nephrin or alterations in nephrin causing massive proteinuria in patients with congenital nephrotic syndrome. Given the importance of nephrin to the structural integrity of the glomerular filtration barrier, we postulated that it might also be altered in acquired forms of nephrotic syndrome (NS). To test this hypothesis, frozen kidney biopsy sections from 29 pediatric patients with acquired NS and 5 controls were examined for expression of nephrin. The pathological diagnoses were minimal change disease (MCNS) (19) and focal segmental glomerulosclerosis (FSGS) (10). To determine if nephrin expression differed between children and adults with NS, 10 adult patients and 3 controls were also examined. Nephrin expression was evaluated by immunoperoxidase staining with a monoclonal antibody against the extracellular FnIII portion of human nephrin. In all cases, nephrin expression was seen along the glomerular basement membrane in a finely granular/linear pattern. Expression of nephrin was similar to controls in all 19 patients with MCNS and all 10 patients with FSGS. Areas of sclerosis in patients with FSGS did not demonstrate nephrin expression. A distinctly granular pattern to nephrin expression was seen in adult patients with NS as well as controls. These findings suggest that an alteration in nephrin expression is not a feature of acquired forms of NS in childhood.

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

Similar content being viewed by others

References

  1. Chesney RW (1999) The idiopathic nephrotic syndrome. Curr Opin Pediatr 11:158–161

    Article  CAS  PubMed  Google Scholar 

  2. 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 

  3. Smoyer WE, Mundel P (1998) Regulation of podocyte structure during the development of nephrotic syndrome. J Mol Med 76:172–183

    Article  CAS  PubMed  Google Scholar 

  4. Tryggvason K (1999) Unraveling the mechanisms of glomerular ultrafiltration: nephrin, a key component of the slit diaphragm. J Am Soc Nephrol 10:2440–2445

    CAS  PubMed  Google Scholar 

  5. Ruotsalainen V, Ljungberg P, Wartiovaara J, Lenkkeri U, Kestila M, Jalanko H, Holmberg C, Tryggvason K (1999) Nephrin is specifically located at the slit diaphragm of glomerular podocytes. Proc Natl Acad Sci U S A 96:7962–7967

    Article  CAS  PubMed  Google Scholar 

  6. Ruotsalainen V, Patrakka J, Tissari P, Reponen P, Hess M, Kestila M, Holmberg C, Salonen R, Heikinheimo M, Wartiovaara J, Tryggvason K, Jalanko H (2000) Role of nephrin in cell junction formation in human nephrogenesis. Am J Pathol 157:1905–1916

    CAS  PubMed  Google Scholar 

  7. Patrakka J, Ruotsalainen V, Ketola I, Holmberg C, Heikinheimo M, Tryggvason K, Jalanko H (2001) Expression of nephrin in pediatric kidney diseases. J Am Soc Nephrol 12:289–296

    CAS  PubMed  Google Scholar 

  8. Furness PN, Hall LL, Shaw JA, Pringle JH (1999) Glomerular expression of nephrin is decreased in acquired human nephrotic syndrome. Nephrol Dial Transplant 14:1234–1237

    CAS  PubMed  Google Scholar 

  9. Doublier S, Ruotsalainen V, Salvidio G, Lupia E, Biancone L, Conaldi PG, Reponen P, Tryggvason K, Camussi G (2001) Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome. Am J Pathol 158:1723–1731

    PubMed  Google Scholar 

  10. Luimula P, Aaltonen P, Ahola H, Palmen T, Holthofer H (2000) Alternatively spliced nephrin in experimental glomerular disease of the rat. Pediatr Res 48:759–762

    CAS  PubMed  Google Scholar 

  11. Rantanen M, Palmen T, Patari A, Ahola H, Lehtonen S, Astrom E, Floss T, Vauti F, Wurst W, Ruiz P, Kerjaschki D, Holthofer H (2002) Nephrin TRAP mice lack slit diaphragms and show fibrotic glomeruli and cystic tubular lesions. J Am Soc Nephrol 13:1586–1594

    CAS  PubMed  Google Scholar 

  12. Yuan H, Takeuchi E, Taylor G A, McLaughlin M, Brown D, Salant DJ (2002) Nephrin dissociates from actin, and its expression is reduced in early experimental membranous nephropathy. J Am Soc Nephrol 13:946–956

    CAS  PubMed  Google Scholar 

  13. Mobassaleh M, Donohue-Rolfe A, Jacewicz M, Grand RJ, Keusch GT (1988) Pathogenesis of shigella diarrhea: evidence for a developmentally regulated glycolipid receptor for shigella toxin involved in the fluid secretory response of rabbit small intestine. J Infect Dis 157:1023–1031

    CAS  PubMed  Google Scholar 

  14. Mobassaleh M, Gross SK, McCluer RH, Donohue-Rolfe A, Keusch GT (1989) Quantitation of the rabbit intestinal glycolipid receptor for Shiga toxin. Further evidence for the developmental regulation of globotriaosylceramide in microvillus membranes. Gastroenterology 97:384–391

    CAS  PubMed  Google Scholar 

  15. Mobassaleh M, Koul O, Mishra K, McCluer RH, Keusch GT (1994) Developmentally regulated Gb3 galactosyltransferase and alpha-galactosidase determine Shiga toxin receptors in intestine. Am J Physiol 267:G618–G624

    CAS  PubMed  Google Scholar 

  16. Kim KB, Hong KH, Kim HJ, Lee SH (2002) Differential expression of nephrin in acquired human proteinuric diseases. Am J Kidney Dis 40:964–973

    Article  CAS  PubMed  Google Scholar 

  17. Wernerson A, Dunér F, Pettersson E, Widholm SM, Berg U, Ruotsalainen V, Tryggvason K, Hultenby K, Söderberg M (2003) Altered ultrastructural distribution of nephrin in minimal change nephrotic syndrome. Nephrol Dial Transplant 18:70–76

    Article  CAS  PubMed  Google Scholar 

  18. Liu L, Done SC, Khoshnoodi J, Bertorello A, Wartiovaara J, Berggren PO, Tryggvason K (2001) Defective nephrin trafficking caused by missense mutations in the NPHS1 gene: insight into the mechanisms of congenital nephrotic syndrome. Hum Mol Genet 10:2637–2644

    Article  CAS  PubMed  Google Scholar 

  19. Tryggvason K (2001) Nephrin: role in normal kidney and in disease. Adv Nephrol Necker Hosp 31:221–234

    CAS  PubMed  Google Scholar 

  20. Schwarz K, Simons M, Reiser J, Saleem M A, Faul C, Kriz W, Shaw AS, Holzman LB, Mundel P (2001) Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin. J Clin Invest 108:1621–1629

    Article  CAS  PubMed  Google Scholar 

  21. Huber TB, Kottgen M, Schilling B, Walz G, Benzing T (2001) Interaction with podocin facilitates nephrin signaling. J Biol Chem 276:41543–41546

    Article  CAS  PubMed  Google Scholar 

  22. Tsukaguchi H, Yager H, Dawborn J, Jost L, Cohlmia J, Abreu PF, Pereira AB, Pollak MR (2000) A locus for adolescent and adult onset familial focal segmental glomerulosclerosis on chromosome 1q25-31. J Am Soc Nephrol 11:1674–1680

    CAS  PubMed  Google Scholar 

  23. Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A, Dahan K, Gubler MC, Niaudet P, Antignac C (2000) NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet 24:349–354

    Article  CAS  PubMed  Google Scholar 

  24. Shih NY, Li J, Karpitskii V, Nguyen A, Dustin ML, Kanagawa O, Miner JH, Shaw AS (1999) Congenital nephrotic syndrome in mice lacking CD2-associated protein. Science 286:312–315

    Article  CAS  PubMed  Google Scholar 

  25. Kaplan JM, Kim SH, North KN, Rennke H, Correia LA, Tong HQ, Mathis BJ, Rodriguez-Perez JC, Allen PG, Beggs AH, Pollak MR (2000) Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nat Genet 24:251–256

    Article  CAS  PubMed  Google Scholar 

  26. Lehtonen S, Zhao F, Lehtonen E (2002) CD2-associated protein directly interacts with the actin cytoskeleton. Am J Physiol Renal Physiol 283:F734–F743

    PubMed  Google Scholar 

  27. Huh W, Kim DJ, Kim MK, Kim YG, Oh HY, Ruotsalainen V, Tryggvason K (2002) Expression of nephrin in acquired human glomerular disease. Nephrol Dial Transplant 17:478–484

    Article  CAS  PubMed  Google Scholar 

  28. Srivastava T, Whiting JM, Garola RE, Dasouki MJ, Ruotsalainen V, Tryggvason K, Hamed R, Alon US (2001) Podocyte proteins in Galloway-Mowat syndrome. Pediatr Nephrol 16:1022–1029

    Article  CAS  PubMed  Google Scholar 

  29. Wang SX, Rastaldi MP, Patari A, Ahola H, Heikkila E, Holthofer H (2002) Patterns of nephrin and a new proteinuria-associated protein expression in human renal diseases. Kidney Int 61:141–147

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The antibodies used in this study were kindly provided by Dr. Vesa Ruotsalainen, Oulu, Finland. This work was supported in part by grants from the National Institutes of Health DK07662 (S.R.H.), DK54500 (A.A.E.), and DK4757 (A.A.E.), the National Kidney Foundation and American Society of Nephrology and Renal Physicians Association (S.R.H.). We would also like to thank Marena Hawk for her administrative assistance in preparing this manuscript.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Washington and Children’s Hospital and Regional Medical Center, Seattle, Washington, USA

    Sangeeta R. Hingorani, Ruth A. McDonald & Allison A. Eddy

  2. Department of Pathology, University of Washington and Children’s Hospital and Regional Medical Center, Seattle, Washington, USA

    Laura S. Finn & Jolanta Kowalewska

Authors
  1. Sangeeta R. Hingorani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura S. Finn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jolanta Kowalewska
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ruth A. McDonald
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Allison A. Eddy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sangeeta R. Hingorani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hingorani, S.R., Finn, L.S., Kowalewska, J. et al. Expression of nephrin in acquired forms of nephrotic syndrome in childhood. Pediatr Nephrol 19, 300–305 (2004). https://doi.org/10.1007/s00467-003-1346-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-003-1346-3

Keywords

Search

Navigation