Pediatric Nephrology

, Volume 6, Issue 1, pp 10–15 | Cite as

The glycosaminoglycan content of renal basement membranes in the congenital nephrotic syndrome of the Finnish type

  • L. P. W. J. Van den Heuvel
  • J. Van den Born
  • H. Jalanko
  • C. H. Schröder
  • J. H. Veerkamp
  • K. J. M. Assmann
  • J. H. M. Berden
  • C. Holmberg
  • J. Rapola
  • L. A. H. Monnens
Original Article

Abstract

A decrease in the concentration of heparan sulphate proteoglycan (HSPG) in the glomerular basement membrane (GBM) is supposed to cause the increased GBM permeability in the congenital nephrotic syndrome (CNS). Therefore, we analysed the glycosaminoglycan (GAG) content and composition of the GBM and tubular basement membrane (TBM) from 3 patients with CNS of the Finnish type (FCNS) and 16 control infants. The GAG content, determined by spectrophotometric assay after papain digestion, was not significantly different in FCNS patients compared with controls. In addition, the GAG composition was comparable in the two groups, with heparan sulphate (HS) constituting at least 75% of the total GAG content. The urinary GAG content (expressed as mg GAG/mmol creatinine) was age dependent, but similar in both groups. Indirect immunofluorescence studies on kidney tissue from normal human infants, using monoclonal or polyclonal antibodies against the core protein of human GBM HSPG, showed linear staining of almost all renal basement membranes. A monoclonal antibody directed against the HS chain of HSPG showed strong GBM and a weak TBM staining. Kidney tissue from three patients with FCNS displayed no discernible differences in the distribution or quality of staining with the same antibodies. These biochemical and immunohistochemical results are in contrast to the decrease in anionic sites (by polyethyleneimine staining) and the replacement of GBM HS by chondroitin sulphate, observed by others in CNS of the diffuse mesangial sclerosis type.

Key words

Congenital nephrotic syndrome Finnish type Glomerular basement membrane Heparan sulphate Heparan sulphate proteoglycan 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Steffensen GK, Nielsen KF (1990) Nephrotic syndrome in the first three months of life. Clin Nephrol Urol 10: 1–7Google Scholar
  2. 2.
    Rapola J (1987) Congenital nephrotic syndrome. Pediatr Nephrol 1: 441–446PubMedGoogle Scholar
  3. 3.
    Ryynänen M, Seppälä M, Kuusela J, Rapola J, Aula P, Seppä A, Jokela V, Castren O (1983) Antenatal screening for congenital nephrosis in Finland by maternal serum alfa-fetoprotein. Br J Obstet Gynaecol 90: 437–442PubMedGoogle Scholar
  4. 4.
    Norio R (1966) Heredity in the congenital nephrotic syndrome. Ann Paediatr Fenn 27: 1–94Google Scholar
  5. 5.
    Autio-Harmainen H (1981) Renal pathology of fetuses with congenital nephrotic syndrome of the Finnish type. A qualitative and quantitative electron microscopic study. Acta Pathol Microbiol Scand 89: 215–222Google Scholar
  6. 6.
    Autio-Harmainen H, Rapola J (1983) The thickness of the glomerular basement membrane in congenital nephrotic syndrome of the Finnish type. Nephron 34: 48–50PubMedGoogle Scholar
  7. 7.
    Tryggvason K (1977) Composition of the glomerular basement membrane in the congenital nephrotic syndrome of the Finnish type. Eur J Clin Invest 7: 177–180PubMedGoogle Scholar
  8. 8.
    Rapola J, Sariola H, Ekblom P (1984) Pathology of fetal congenital nephrosis: immunohistochemical and ultrastructural studies. Kidney Int 25: 701–707PubMedGoogle Scholar
  9. 9.
    Autio-Harmainen H, Karttunen T, Risteli L, Risteli J, Rapola J (1985) Accumulation of laminin and type IV collagen in the kidney in congenital nephrosis. Kidney Int 27: 661–667Google Scholar
  10. 10.
    Caulfield JP, Farquhar M (1978) Loss of anionic sites from the glomerular basement membrane in aminonucleoside nephrosis. Lab Invest 39: 505–512PubMedGoogle Scholar
  11. 11.
    Olsen JL, Rennke HG, Venkatachalam MA (1981) Alterations in the charge and size selectivity barrier of the glomerular filter in aminonucleoside nephrosis in rats. Lab Invest 44: 271–278PubMedGoogle Scholar
  12. 12.
    Mynderse LA, Hassell JR, Kleinman HK, Martin GR, Hernandez AN (1983) Loss of heparan sulfate proteoglycan from glomerular basement membrane of nephrotic rats. Lab Invest 48: 292–302PubMedGoogle Scholar
  13. 13.
    Groggel GC, Hovingh P, Border WA, Linker A (1987) Changes in glomerular heparan sulfate in puromycin aminonucleoside nephrosis. Am J Pathol 128: 521–527PubMedGoogle Scholar
  14. 14.
    Vernier RL, Klein DJ, Sisson SP, Mahan JD, Oegema TR, Brown DM (1983) Heparan sulfate-rich anionic sites in human glomerular basement membrane. Decreased concentration in congenital nephrotic syndrome. N Engl J Med 309: 1001–1009PubMedGoogle Scholar
  15. 15.
    Okada K, Kawakami K, Miyao M, Oite T (1986) Ultrastructural alterations of glomerular anionic sites in idiopathic membranous glomerulonephritis. Clin Nephrol 26: 7–14PubMedGoogle Scholar
  16. 16.
    Okada K, Kawakami K, Miyao M, Funai M, Kagami S, Kuroda Y, Oite T (1989) Ultrastructural alterations of glomerular anionic sites in IgA nephropathy. Clin Nephrol 31: 96–102PubMedGoogle Scholar
  17. 17.
    Vermylen C, Levin M, Mossman J, Barratt TM (1989) Reduced heparan sulfate content of glomerular basement membrane and increased urinary excretion in congenital nephrotic syndrome. Pediatr Nephrol 3: 122–129PubMedGoogle Scholar
  18. 18.
    Kanwar YS (1984) Biology of disease. Biophysiology of glomerular filtration and proteinuria. Lab Invest 51: 7–21PubMedGoogle Scholar
  19. 19.
    Van den Heuvel LPWJ, Van den Born J, Van de Velden TJAM, Veerkamp JH, Monnens LAH, Schröder CH, Berden JHM (1989) Isolation and partial characterization of heparan sulfate proteoglycan from the human glomerular basement membrane. Biochem J 264: 457–465PubMedGoogle Scholar
  20. 20.
    Van den Born J, Van den Heuvel LPWJ, Bakker MAH, Veerkamp JH, Assmann KJM, Berden JHM (1990) Monoclonal antibodies against human glomerular and GBM heparan sulfate proteoglycan. Characterization and distribution studies in normal tissues and glomerulopathies (abstract). Kidney Int 37: 445Google Scholar
  21. 21.
    Van den Born J, Van den Heuvel LPWJ, Bakker MAH, Veerkamp JH, Assmann KJM, Berden JHM (1990) Production, characterization and nephritogenicity of a monoclonal antibody against glomerular heparan sulfate (abstract). Kidney Int 38: 1230Google Scholar
  22. 22.
    Langeveld JPM, Veerkamp JH (1981) Chemical characterization of glomerular and tubular basement membranes of various mammalian species. Comp Biochem Physiol [B] 68: 31–40Google Scholar
  23. 23.
    Langeveld JPM, Veerkamp JH, Duyf CPM, Monnens LAH (1981) Chemical characterization of glomerular and tubular basement membranes of different ages. Kidney Int 20: 104–114PubMedGoogle Scholar
  24. 24.
    Farndale RW, Buttle DJ, Barrett AJ (1986) Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta 883: 173–177PubMedGoogle Scholar
  25. 25.
    Reubsaet FAG, Langeveld JPM, Veerkamp JH (1985) Glycosaminoglycan content of glomerular and tubular basement membranes of various mammalian species. Biochim Biophys Acta 838: 144–150PubMedGoogle Scholar
  26. 26.
    Van den Heuvel LPWJ, Van den Born J, Veerkamp JH, Van de Velden TJAM, Schenkels L, Monnens LAH, Schröder CH, Berden JHM (1990) Heparan sulfate proteoglycan from human tubular basement membrane. Comparison with this component from the glomerular basement membrane. Biochim Biophys Acta 1025: 67–76PubMedGoogle Scholar
  27. 27.
    Rennard SI, Berg R, Martin GR, Foidart JM, Gehron Robey P (1980) Enzyme-linked immunoassay (ELISA) for connective tissue components. Anal Biochem 104: 205–214PubMedGoogle Scholar
  28. 28.
    Faaber P, Capel PJA, Rijke GPM, Vierwinden G, Van de Putte LBA, Koene RAP (1984) Cross-reactivity of anti-DNA antibodies with proteoglycans. Clin Exp Immunol 55: 502–508PubMedGoogle Scholar
  29. 29.
    Reubsaet FAG, Veerkamp JH, Monnens LAH (1985) Sulfated glycosaminoglycan content of glomerular and tubular basement membranes of individuals of different ages. Nephron 41: 344–347PubMedGoogle Scholar
  30. 30.
    Michelacci YM, Glashan RQ, Schor N (1989) Urinary excretion of glycosaminoglycans in normal and stone forming subjects. Kidney Int 36: 1022–1028PubMedGoogle Scholar
  31. 31.
    Staprans I, Garon SJ, Hopper J, Felts JM (1981) Characterization of glycosaminoglycans in urine from patients with nephrotic syndrome and control subjects, and their effect on lipoprotein lipase. Biochim Biophys Acta 678: 414–422PubMedGoogle Scholar
  32. 32.
    Klein DJ, Oegema TR, Eisenstein R, Furcht L, Michael AF, Brown DM (1983) Renal localization of heparan sulfate proteoglycan by immunohistochemistry. Am J Pathol 111: 323–330PubMedGoogle Scholar
  33. 33.
    Quatacker J (1986) Alterations in the sialic acid content of the rat glomerular filter in aminonucleoside nephrosis. Virchows Arch [B] 50: 237–249Google Scholar
  34. 34.
    Bertolatus JA (1990) Affinity labeling of glomerular basement membrane anionic sites using specific biotinylation and colloidal probes. J Histochem Cytochem 38: 377–384PubMedGoogle Scholar
  35. 35.
    Sperl W, Gruber W, Quatacker J, Monnens L, Thoenes W, Fink F, Paschke E (1990) Nephrosis in two siblings with infantile sialic acid storage disease. Eur J Pediatr 149: 477–482PubMedGoogle Scholar
  36. 36.
    Kanwar YS, Jakubowski ML (1984) Unaltered anionic sites of glomerular basement membrane in aminonucleoside nephrosis. Kidney Int 25: 613–618PubMedGoogle Scholar
  37. 37.
    Lelongt B, Makino H, Kanwar YS (1987) Status of glomerular proteoglycans in aminonucleoside nephrosis. Kidney Int 31: 1299–1311PubMedGoogle Scholar
  38. 38.
    Groggel GC, Hovingh P, Border WA, Linker A (1987) Changes in glomerular heparan sulfate in puromycin aminonucleoside nephrosis. Am J Pathol 128: 521–527PubMedGoogle Scholar

Copyright information

© IPNA 1992

Authors and Affiliations

  • L. P. W. J. Van den Heuvel
    • 1
  • J. Van den Born
    • 2
  • H. Jalanko
    • 5
  • C. H. Schröder
    • 3
  • J. H. Veerkamp
    • 1
  • K. J. M. Assmann
    • 4
  • J. H. M. Berden
    • 2
  • C. Holmberg
    • 5
  • J. Rapola
    • 6
  • L. A. H. Monnens
    • 3
  1. 1.Department of BiochemistryUniversity of NijmegenNijmegenThe Netherlands
  2. 2.Department of NephrologyUniversity of NijmegenNijmegenThe Neherlands
  3. 3.Department of PaediatricsUniversity of NijmegenNijmegenThe Netherlands
  4. 4.Department of PathologyUniversity of NijmegenNijmegenThe Netherlands
  5. 5.Department of PaediatricsUniversity of HelsinkiHelsinkiFinland
  6. 6.Department of PathologyUniversity of HelsinkiHelsinkiFinland

Personalised recommendations