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Sequential ultrastructural podocytic lesions and development of proteinuria in serum sickness nephritis in the rat

Virchows Archiv A volume 417, pages 279–290 (1990)Cite this article

Summary

Serum sickness nephritis was induced in Fisher rats by immunization with egg albumin (EA) and correlations between immune complex deposition, alterations of podocytes and development of proteinuria were analysed. Immunoelectron microscopy showed that EA, rat IgG and C3 were confined to the electron-dense deposits (Ds). From 3 weeks, when significant proteinuria had developed, the subepithelial region was filled with large numbers of Ds on the peripheral capillary wall as well as in the paramesangium. The loss of slit diaphragms and detachment of foot processes overlying Ds were observed and the escape of Ds into urinary space was frequently detected. Morphometric evaluation showed that the volume of subepithelial Ds and the number of the sites of podocytic detachment correlate significantly with the amount of proteinuria. In addition, the native ferritin injected via the abdominal aorta was seen in large amounts in the urinary space near the areas devoid of epithelial covering. The development of podocytic detachment was clearly coincident with the appearance of proteins with a larger molecular weight in urine. From these results, it is suggested that the loss of slit diaphragms and the detachment of podocytes resulting from the progressive accumulation of Ds will allow the leakage of proteins of larger molecular weight across the capillary wall. These podocytic lesions may be one of the main aetiologies for the development of heavy proteinuria in this model.

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References

  • Adler S, Salant DJ, Dittmer JE, Rennke HG, Madaio MP, Couser WG (1983) Mediation of proteinuria in membranous nephropathy due to a planted glomerular antigen. Kidney Int 23:807–815

    Google Scholar 

  • Bendayan M, Zollinger M (1983) Ultrastructural localization of antigenic sites on osmium-fixed tissues applying the protein A-gold technique. J Histochem Cytochem 31:101–109

    Google Scholar 

  • Caulfield JP, Reid JJ, Farquhar MG (1976) Alterations of glomerular epithelium in acute aminonucleoside nephrosis: evidence for formation of occluding junctions and epithelial detachment. Lab Invest 34:43–59

    Google Scholar 

  • Fraij BM (1989) Separation and identification of urinary proteins and stone-matrix proteins by mini-slab sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Clin Chem 35:658–662

    Google Scholar 

  • Fries JWU, Mendrick DL, Rennke HG (1988) Determinants of immune complex-mediated glomerulonephritis. Kidney Int 34:333–345

    Google Scholar 

  • Furness PN, Turner SN, Appleby P, Turner DR (1989) A morphological study of experimental proteinuria using a novel form of surface fixation. J Pathol 157:37–45

    Google Scholar 

  • Hearn SA, Silver MM, Sholdice JA (1985) Immunoelectron microscopic labeling of immunoglobulin in plasma cells after osmium fixation and epoxy embedding. J Histochem Cytochem 33:1212–1218

    Google Scholar 

  • Kanwar YS (1984) Biology of disease. Biophysiology of glomerular filtration and proteinuria. Lab Invest 51:7–21

    Google Scholar 

  • Kanwar YS, Farquhar MG (1980) Detachment of endothelium and epithelium from the glomerular basement membrane produced by kidney perfusion with neuraminidase. Lab Invest 42:375–384

    Google Scholar 

  • Kanwar YS, Rosenzweig LJ (1982) Altered glomerular permeability as a result of focal detachment of visceral epithelium. Kidney Int 21:565–574

    Google Scholar 

  • Kelley VE, Cavallo T (1977) Glomerular permeability. Ultrastructural studies in New Zealand Black/White mice using polyanionic ferritin as a molecular probe. Lab Invest 37:265–275

    Google Scholar 

  • Kelley VE, Cavallo T (1978) Glomerular permeability. Transfer of native ferritin in glomeruli with decreased anionic sites. Lab Invest 39:547–553

    Google Scholar 

  • Kelley VE, Cavallo T (1980) Glomerular permeability. Focal loss of anionic sites in glomeruli of proteinuric mice with lupus nephritis. Lab Invest 42:59–64

    Google Scholar 

  • Koyama A, Niwa Y, Shigematsu H, Taniguchi M, Tada T (1978) Studies on passive serum sickness. II. Factors determining the localization of antigen-antibody complexes in the murine renal glomerulus. Lab Invest 38:253–262

    Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Google Scholar 

  • McCluskey RT (1983) Immunologic mechanisms in glomerular disease. In: Heptinstall RH (ed) Pathology of kidney. Little Brown, Boston, pp 301–386

    Google Scholar 

  • Messina A, Davies DJ, Dillane PC, Ryan GB (1987) Glomerular epithelial abnormalities associated with the onset of proteinuria in aminonucleoside nephrosis. Am J Pathol 126:220–229

    Google Scholar 

  • Olson 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 44:271–279

    Google Scholar 

  • Ryan GB, Karnovsky MJ (1975) An ultrastructural study of the mechanisms of proteinuria in aminonucleoside nephrosis. Kidney Int 8:219–232

    Google Scholar 

  • Ryan GB, Leventhal M, Karnovsky MJ (1975a) A freeze-fracture study of the junctions between glomerular epithelial cells in aminonucleoside nephrosis. Lab Invest 32:397–403

    Google Scholar 

  • Ryan GB, Rodewald R, Karnovsky MJ (1975b) An ultrastructural study of the glomerular slit diaphragm in aminonucleoside nephrosis. Lab Invest 33:461–468

    Google Scholar 

  • Ryan GB, Hein SJ, Karnovsky MJ (1976) Glomerular permeability to proteins. Effects of hemodynamic factors on the distribution of endogenous immunoglobulin G and exogenous catalase in the rat glomerulus. Lab Invest 34:415–427

    Google Scholar 

  • Ryan GB, Hein SJ, Karnovsky MJ (1978) The distribution of albumin and immunoglobulin G in the glomerular capillary wall in aminonucleoside nephrosis. Pathology 10:335–341

    Google Scholar 

  • Sawtell NM, Weiss MA, Pesce AJ, Michael JG (1987) An immune complex glomerulopathy associated with glomerular capillary thrombosis in the laboratory mouse: a highly reproducible accelerated model utilizing cationized antigen. Lab Invest 56:256–263

    Google Scholar 

  • Sawtell NM, Hartman AL, Weiss MA, Pesce AJ, Michael JG (1988) C3 dependent, C5 independent immune complex glomerulopathy in the mouse. Lab Invest 58:287–293

    Google Scholar 

  • Schneeberger EE, O'Brien A, Grupe WE (1979) Altered glomerular permeability in Munich-Wistar rats with autologous immune complex nephritis. Lab Invest 40:227–235

    Google Scholar 

  • Shigematsu H, Koyama A (1988a) Suppressive effect of cyclospor-in A on the induction of chronic serum sickness nephritis in the rat. Acta Pathol Jpn 38:11–19

    Google Scholar 

  • Shigematsu H, Koyama A (1988b) Therapeutic effect of cyclosporin A and steroid on serum sickness type nephritis in the rat. I. Suppression of the antibody response and induction of glomerulonephritis. Jpn J Nephrol 30:1109–1114

    Google Scholar 

  • Shigematsu H, Koyama A (1988c) Therapeutic effect of cyclosporin A and steroid on serum sickness type nephritis in the rat. II. Suppressive effect on full-blown proliferative glomerulonephritis. Jpn J Nephrol 30:1115–1122

    Google Scholar 

  • Thaiss F, Batsford S, Mihatsch MJ, Heitz PU, Biter-Suermann D, Vogt A (1986) Mediator systems in a passive model of in situ immune complex glomerulonephritis: role for complement, polymorphonuclear granulocytes and monocytes. Lab Invest 54:624–635

    Google Scholar 

  • Venkatachalam MA, Cotran RS, Karnovsky MJ (1970) An ultrastructural study of glomerular permeability in aminonucleoside nephrosis using catalase as a tracer protein. J Exp Med 132:1168–1180

    Google Scholar 

  • Yamamoto T, Kihara I, Morita T, Oite T (1978) Bovine serum albumin (BSA) nephritis in rats. I. Experimental model. Acta Pathol Jpn 28:859–866

    Google Scholar 

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  1. Department of Pathology, Shinshu University School of Medicine, 3-1-1 Asahi Matsumoto, 390, Nagano, Japan

    Hui-Jun Duan

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  1. Hui-Jun Duan
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Duan, HJ. Sequential ultrastructural podocytic lesions and development of proteinuria in serum sickness nephritis in the rat. Vichows Archiv A Pathol Anat 417, 279–290 (1990). https://doi.org/10.1007/BF01605778

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  • DOI: https://doi.org/10.1007/BF01605778

Key words

  • Serum sickness nephritis
  • Proteinuria
  • Immune complex
  • Podocyte detachment
  • Slit diaphragm