Skip to main content
SpringerLink
Log in

Models of Glomerulonephritis

  • Protocol
Book cover Renal Disease

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 86))

Abstract

Understanding the mechanisms of glomerular injury is critically dependent on the histologic assessment of cellular responses, immune processes, and ultrastructural changes. However, studies of human disease have been limited by a relative lack of tissue sampling. Renal biopsy is often performed only when the diagnosis of glomerular disease cannot be determined based on clinical grounds or in conjunction with indirect markers such as serologies, complement levels, and urine microscopy. Furthermore, a biopsy is typically undertaken upon clinical presentation, thereby providing a mere “snapshot” of the disease. In the absence of serial histologic evaluation, the opportunity to delineate mechanisms of disease progression is limited. However, the use of animal models has overcome a number of these hurdles, thereby advancing our current knowledge and understanding of the pathogenesis of glomerular disease. Animal studies afford the opportunity to study the development, progression, and resolution of disease over time. Furthermore, the host response to injury may be deliberately modified, either generally (as with nonspecific immunosuppressants) or selectively (as with target gene deletions or neutralizing antibodies), thereby providing further insight into pathogenetic mechanisms that cannot be undertaken in man.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Anders, H. J. and Schlondorff, D. (2000) Murine models of renal disease: possibilities and problems in studies using mutant mice. Exp. Nephrol. 8, 181–193.

    Article  PubMed  CAS  Google Scholar 

  2. Wilson, C. B. (1997) Immune models of glomerular injury, (Neilson, E. G. and Couser, W. G., eds.), Lippincott-Raven Publishers, Philadelphia, pp. 729–773.

    Google Scholar 

  3. Hoedemaeker, P. J. and Weening, J. J. (1989) Relevance of experimental models for human nephropathology. Kidney Int. 35, 1015–1025.

    Article  PubMed  CAS  Google Scholar 

  4. Foster, M. H. (1999) Relevance of systemic lupus erythematosus nephritis animal models to human disease. Semin. Nephrol. 19, 12–24.

    PubMed  CAS  Google Scholar 

  5. Peutz-Koostra, C. J., et al. (2001) Lupus nephritis: lessons from experimental animal models. J. Lab. Clin. Med. 137, 244–260.

    Article  Google Scholar 

  6. Ryan, G. B. and Karnovsky, M. J. (1975) An ultrastructural study of the mechanisms of proteinuria in aminonucleoside nephrosis. Kidney Int. 8, 219–232.

    Article  PubMed  CAS  Google Scholar 

  7. Messina, A., et al. (1987) Glomerular epithelial cell abnormalities associated with the onset of proteinuria in aminonucleoside nephrosis. Am. J. Pathol. 126, 220–229.

    PubMed  CAS  Google Scholar 

  8. Grond, J., et al. (1988) Differences in puromycin aminonucleoside nephrosis in two rat strains. Kidney Int. 33, 524–529.

    Article  PubMed  CAS  Google Scholar 

  9. Krishnamurti, U., et al. (2001) Puromycin aminonucleoside suppresses integrin expression in cultured glomerular epithelial cells. J. Am. Soc. Nephrol. 12, 758–766.

    PubMed  CAS  Google Scholar 

  10. Osicka, T. M., Hankin, A. R., and Comper, W. D. (1999) Puromycin aminonucleoside nephrosis results in a marked increase in fractional clearance of albumin. Am. J. Physiol. 277, F139–F145.

    PubMed  CAS  Google Scholar 

  11. Groggel, G. C., et al. (1987) Changes in glomerular heparan sulfate in puromycin aminonucleoside nephrosis. Am. J. Pathol. 128, 521–527.

    PubMed  CAS  Google Scholar 

  12. Kerjaschki, D., Vernillo, A. T., and Farquhar, M. G. (1985) Reduced sialylation of podocalyxin—the major sialoprotein of the rat kidney glomerulus—in aminonucleoside nephrosis. Am. J. Pathol. 118, 343–349.

    PubMed  CAS  Google Scholar 

  13. Eddy, A. and Michael, A. F. (1988) Acute tubulointerstitial nephritis associated with aminonucleoside nephrosis. Kidney Int. 33, 14–23.

    Article  PubMed  CAS  Google Scholar 

  14. Breiteneder-Geleff, S., et al. (1997) Podoplanin, novel 43-kd membrane protein of glomerular epithelial cells, is down-regulated in puromycin nephrosis. Am. J. Pathol. 151, 1141–1152.

    PubMed  CAS  Google Scholar 

  15. Matsui, K., et al. (1999) Podoplanin, a novel 43-kDa membrane protein, controls the shape of podocytes. Nephrol. Dial. Transplant. 14, S9–S11.

    Article  Google Scholar 

  16. Chen, A., et al. (1998) Experimental focal segmental glomerulosclerosis in mice. Nephron 78, 440–452.

    Article  PubMed  CAS  Google Scholar 

  17. Bertani, T., et al. (1982) Adriamycin-induced nephrotic syndrome in rats: sequence of pathologic events. Lab. Investig. 46, 16–23.

    PubMed  CAS  Google Scholar 

  18. Wang, Y., et al. (2000) Progressive adriamycin nephropathy in mice: sequence of histologic and immunohistochemical events. Kidney Int. 58, 1797–1804.

    Article  PubMed  CAS  Google Scholar 

  19. Whiteside, C., et al. (1989) Glomerular epithelial cell detachment, not reduced charge density, correlates with proteinuria in adriamycin and puromycin nephrosis. Lab. Investig. 61, 650–660.

    PubMed  CAS  Google Scholar 

  20. O’Donnell, M. P., et al. (1985) Adriamycin-induced chronic proteinuria: a structural and functional study. J. Lab. Clin. Med. 106, 62–67.

    Google Scholar 

  21. Okuda, S., et al. (1986) Adriamycin-induced nephropathy as a model of chronic progressive glomerular disease. Kidney Int. 29, 502–510.

    Article  PubMed  CAS  Google Scholar 

  22. Song, H., et al. (2000) Glomerulosclerosis in adriamycin-induced nephrosis is accelerated by a lipid-rich diet. Pediatr. Nephrol. 15, 196–200.

    Article  PubMed  CAS  Google Scholar 

  23. Van den Branden, C., et al. (2000) Renal antioxidant enzymes and fibrosis-related markers in the rat adriamycin model. Nephron 86, 167–175.

    Article  PubMed  Google Scholar 

  24. Salant, D., Darby, C., and Couser, W. G. (1980) Experimental Membranous Glomerulonephritis in Rats. J. Clin. Invest. 66, 71–81.

    Article  PubMed  CAS  Google Scholar 

  25. Kerjaschki, D. and Neale, T. J. (1996) Molecular mechanisms of glomerular injury in rat experimental membranous nephropathy (Heymann nephritis). J. Am. Soc. Nephrol. 7, 2518–2526.

    PubMed  CAS  Google Scholar 

  26. Kerjaschki, D., et al. (1989) Transcellular transport and membrane insertion of the c5b-9 membrane attack complex of complement by glomerular epithelial cells in experimental membranous nephropathy. J. Immunol. 143, 546–552.

    PubMed  CAS  Google Scholar 

  27. Couser, W. G., Schulze, M., and Pruchno, C. J. (1992) Role of c5b-9 in experimental membranous nephropathy. Nephrol. Dial. Transplant. Suppl 1, 25–31.

    Google Scholar 

  28. Baker, P. J., et al. (1989) Depletion of c6 prevents development of proteinuria in experimental membranous nephropathy in rats. Am. J. Pathol. 135, 185–194.

    PubMed  CAS  Google Scholar 

  29. Salant, D., et al. (1980) A new role for complement in experimental membranous nephropathy in rats. J. Clin. Invest. 66, 1339–1350.

    Article  PubMed  CAS  Google Scholar 

  30. Quigg, R. J., et al. (1995) Crry and CD59 regulate complement in rat glomerular epithelial cells and are inhibited by the nephritogenic antibody of passive Heymann nephritis. J. Immunol. 154, 3437–3443.

    PubMed  CAS  Google Scholar 

  31. Schiller, B., et al. (1998) Inhibition of complement regulation is key to the pathogenesis of active Heymann nephritis. J. Exp. Med. 188, 1353–1358.

    Article  PubMed  CAS  Google Scholar 

  32. Cunningham, P. N., et al. (2001) Glomerular complement regulation is overwhelmed in passive Heymann nephritis. Kidney Int. 60, 900–909.

    Article  PubMed  CAS  Google Scholar 

  33. Pippin, J. W., Durvasula, R. V., et al. (2003) Complement (C5b-9) induces DNA damage in podocytes in vitro and in vivo: A novel response to sublytic injury. J. Clin. Invest., in press.

    Google Scholar 

  34. Couser, W. G., et al. (1978) Experimental glomerulonephritis in the isolated perfused rat kidney. J. Clin. Investig. 62, 1275–1287.

    Article  PubMed  CAS  Google Scholar 

  35. Jefferson, J. A. and Johnson, R. J. (1999) Experimental mesangial proliferative glomerulonephritis (the anti-Thy-1. 1 model). J. Nephrol. 12, 297–307.

    PubMed  CAS  Google Scholar 

  36. Brandt, J., et al. (1996) Role of complement membrane attack complex (C5b-9) in mediating experimental mesangioproliferative glomerulonephritis. Kidney Int. 49, 335–343.

    Article  PubMed  CAS  Google Scholar 

  37. Shankland, S. J., et al. (1996) Changes in cell-cycle protein expression during experimental mesangial proliferative glomerulonephritis. Kidney Int. 50, 1230–1239.

    Article  PubMed  CAS  Google Scholar 

  38. Pippin, J., et al. (1997) Direct in vivo inhibition of the nuclear cell cycle cascade in experimental mesangial proliferative glomerulonephritis with roscovitine, a novel cyclin-dependent kinase antagonist. J. Clin. Investig. 100, 2512–2520.

    Article  PubMed  CAS  Google Scholar 

  39. Johnson, R. J., et al. (1990) Platelets mediate glomerular cell proliferation in immune complex nephritis induced by anti-mesangial cell antibodies in the rat. Am. J. Pathol. 136, 369–374.

    PubMed  CAS  Google Scholar 

  40. Johnson, R. J., et al. (1992) Inhibition of mesangial cell proliferation and matrix expansion in glomerulonephritis in the rat by antibody to platelet-derived growth factor. J. Exp. Med. 175, 1413–1416.

    Article  PubMed  CAS  Google Scholar 

  41. Fukuda, K., et al. (1996) Role of endothelin as a mitogen in experimental glomerulonephritis in rats. Kidney Int. 49, 1320–1329.

    Article  PubMed  CAS  Google Scholar 

  42. Haseley, L. A., et al. (1999) Dissociation of mesangial cell migration and proliferation in experimental glomerulonephritis. Kidney Int. 56, 964–972.

    Article  PubMed  CAS  Google Scholar 

  43. Johnson, R. J., et al. (1991) Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. J. Clin. Invest. 87, 847–858.

    Article  PubMed  CAS  Google Scholar 

  44. Border, W. A., et al. (1990) Suppression of experimental glomerulonephritis by antiserum against transforming growth factor β1. Nature 346, 371–374.

    Article  PubMed  CAS  Google Scholar 

  45. Shimizu, A., et al. (1995) Apoptosis in the repair process of experimental proliferative glomerulonephritis. Kidney Int. 47, 114–121.

    Article  PubMed  CAS  Google Scholar 

  46. Morita, T., Yamamoto, T., and Churg, J. (1998) Mesangiolysis: an update. American Journal of Kidney Diseases 31, 559–573.

    Article  PubMed  CAS  Google Scholar 

  47. Nakao, N., et al. (1998) Tenascin-C promotes healing of Habu-Snake venom-induced glomerulonephritis. Am. J. Pathol. 152, 1237–1245.

    PubMed  CAS  Google Scholar 

  48. Cattell, V. and Bradfield, J. W. (1977) Focal mesangial proliferative glomerulonephritis in the rat caused by Habu snake venom. Am. J. Pathol. 87, 511–524.

    PubMed  CAS  Google Scholar 

  49. Barnes, J. L. and Abboud, H. E. (1993) Temporal expression of autocrine growth factors corresponds to morphological features of mesangial proliferation in habu snake venom-induced glomerulonephritis. Am. J. Pathol. 143, 1366–1376.

    PubMed  CAS  Google Scholar 

  50. Barnes, J. L., Hastings, R. R., and De La Garza, M. (1994) Sequential expression of cellular fibronectin by platelets, macrophages, and mesangial cells in proliferative glomerulonephritis. Am. J. Pathol. 145, 585–597.

    PubMed  CAS  Google Scholar 

  51. Barnes, J. L. (1989) Amelioration of Habu venom-induced glomerular lesions: Potential role for platelet secretory proteins. J. Lab. Clin. Med. 114, 200–206.

    PubMed  CAS  Google Scholar 

  52. Cattell, V. and Mehotra, A. (1980) Effect of anti-platelet medications on Habu snake venom nephritis. Br. J. Exp. Pathol. 61, 310–314.

    PubMed  CAS  Google Scholar 

  53. Masuda, Y., et al. (2001) Vascular endothelial growth factor enhances glomerular capillary repair and accelerates resolution of experimentally induced glomerulonephritis. Am. J. Pathol. 159, 599–608.

    Article  PubMed  CAS  Google Scholar 

  54. Nangaku M, et al. (1998) A new model of renal microvascular injury. Curr. Opin. Nephrol. Hypertens. 7, 457–462.

    PubMed  CAS  Google Scholar 

  55. Nangaku, M., et al. (1997) A new model of renal microvascular endothelial injury. Kidney Int. 52, 182–194.

    Article  PubMed  CAS  Google Scholar 

  56. Nangaku, M., et al. (1998) CD59 protects glomerular endothelial cells from immune-mediated thrombotic microangiopathy in rats. J. Am. Soc. Nephrol. 9, 590–597.

    PubMed  CAS  Google Scholar 

  57. Shao, J., et al. (2001) Protective role of nitric oxide in a model of thrombotic microangiopathy in rats. J. Am. Soc. Nephrol. 12, 2088–2097.

    PubMed  CAS  Google Scholar 

  58. Suga, S., et al. (2001) Vascular endothelial growth factor (VEGF 121) pro-tects rats from renal infarction in thrombotic microangiopathy. Kidney Int. 60, 1297–1308.

    Article  PubMed  CAS  Google Scholar 

  59. Kang, D. H., et al. (2002) Role of microvacular endothelium in progressive renal disease. J. Am. Soc. Nephrol. 13, 806–816.

    Article  PubMed  Google Scholar 

  60. Allison, M. E., Wilson, C. B., and Gottschalk, C. W. (1974) Pathophysiology of experimental glomerulonephritis in rats. J. Clin. Invest. 53, 1402–1423.

    Article  PubMed  CAS  Google Scholar 

  61. Germuth, F. G., et al. (1978) Antibasement membrane disease. II. Mechanism of glomerular injury in an accelerated model of Masugi nephritis. Lab. Investig. 39, 421–429.

    PubMed  Google Scholar 

  62. Lan, H. Y., et al. (1997) Local macrophage proliferation in the pathogenesis of glomerular crescent formation in rat anti-glomerular basement membrane (GBM) glomerulonephritis. Clin. Exp. Immunol. 110, 233–240.

    Article  PubMed  CAS  Google Scholar 

  63. Steblay, R. and Rudofsky, U. (1968) In vitro and in vivo properties of autoantibodies eluted from kidneys of sheep with autoimmune glomerulonephritis. Nature 218, 1269–1271.

    Article  PubMed  CAS  Google Scholar 

  64. Moorthy, A. V. and Abreo, K. (1983) potentiation of nephrotoxic serum nephritis in Lewis rats by Freund’s complete adjuvant—possible role for cellular immune mechanisms. Clin. Immunol. Immunopathol. 28, 383–394.

    Article  PubMed  CAS  Google Scholar 

  65. Kalluri, R., et al. (1997) Susceptibility to anti-glomerular basement membrane disease and Goodpasture syndrome is linked to MHC class II genes and the emergence of T cell-mediated immunity in mice. J. Clin. Investig. 100, 2263–2275.

    Article  PubMed  CAS  Google Scholar 

  66. Reynolds, J., et al. (2000) CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis. J. Clin. Invest. 105, 643–651.

    Article  PubMed  CAS  Google Scholar 

  67. Reynolds, J., et al. (2002) Anti-CD8 monoclonal antibody therapy is effective in the prevention and treatment of experimental autoimmune glomerulonephritis. J. Am. Soc. Nephrol. 13, 359–369.

    PubMed  CAS  Google Scholar 

  68. Quigg, R. J., et al. (1998) Transgenic mice overexpressing the complement inhibitor crry as a soluble protein are protected from antibody-induced glomerular injury. J. Exp. Med. 188, 1321–1331.

    Article  PubMed  CAS  Google Scholar 

  69. Janssen, U., et al. (1998) Improved survival and amelioration of nephrotoxic nephritis in intercellular adhesion molecule-1 knockout mice. J. Am. Soc. Nephrol. 9, 1805–1814.

    PubMed  CAS  Google Scholar 

  70. Shimamura, T. and Morrison, A. B. (1975) A progressive glomerulosclerosis occurring in partial five-sixths nephrectomized rats. Am. J. Pathol. 79, 95–106.

    PubMed  CAS  Google Scholar 

  71. Faraj, A. H. and Morley, A. R. (1992) Remnant kidney pathology after five-sixth nephrectomy in rat. APMIS 100, 1097–1105.

    Article  PubMed  CAS  Google Scholar 

  72. Griffin, K., Picken, M., and Bidani, A. K. (1994) Method of renal mass reduction is a critical modulator of subsequent hypertension and glomerular injury. J. Am. Soc. Nephrol. 4, 2023–2031.

    PubMed  CAS  Google Scholar 

  73. Hostetter, T., et al. (1981) Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am. J. Physiol. 241, F85–F93.

    PubMed  CAS  Google Scholar 

  74. Brown, S. A. and Brown, C. A. (1995) Single nephron adaptation to partial renal ablation in cats. Am. J. Physiol. 269, R1002–R1008.

    PubMed  CAS  Google Scholar 

  75. Brenner, B. M., Lawler, E. V., and Mackenzie, H. S. (1996) The hyperfiltration theory: a paradigm shift in nephrology. Kidney Int. 49, 1774–1777.

    Article  PubMed  CAS  Google Scholar 

  76. Floege, J., et al. (1992) Glomerular cells, extracellular matrix accumulation, and the development of glomerulosclerosis in the remnant kidney model. Lab. Investig. 66, 485–496.

    PubMed  CAS  Google Scholar 

  77. Brochu, E., et al. (1999) Endothelin ET-A receptor blockade prevents the progression of renal failure and hypertension in uraemic rats. Nephrol. Dial. Transplant. 14, 1881–1888.

    Article  PubMed  CAS  Google Scholar 

  78. Junaid, A., Hostetter, T., and Rosenberg, M. E. (1997) Interaction of angiotensin II and TGF-β1 in the rat remnant kidney. J. Am. Soc. Nephrol. 8, 1732–1738.

    PubMed  CAS  Google Scholar 

  79. Romero, F., et al. (1999) Mycophenolate mofetil prevents the progressive renal failure induced by 5/6 renal ablation in rats. Kidney Int. 55, 945–955.

    Article  PubMed  CAS  Google Scholar 

  80. Schrier, R. W., et al. (1994) Increased nephron oxygen consumption: Potential role in progression of chronic renal disease. American Journal of Kidney Diseases 23, 176–182.

    PubMed  CAS  Google Scholar 

  81. Yano, N., et al. (2000) Genomic repertoire of human mesangial cells: comprehensive analysis of gene expression by cDNA array hybridization. Nephrology 5, 215–223.

    Article  CAS  Google Scholar 

  82. Kurella, M., et al. (2001) DNA microarray analysis of complex biologic processes. J. Am. Soc. Nephrol. 12, 1072–1078.

    PubMed  CAS  Google Scholar 

  83. Knepper, M. A. (2002) Proteomics and the kidney. J. Am. Soc. Nephrol. 13, 1398–1408.

    Article  PubMed  CAS  Google Scholar 

  84. Topham, P. S., et al. (1999) Nephritogenic mAb 5-1-6 is directed at the extracellular domain of rat nephrin. J. Clin. Invest. 104, 1559–1566.

    Article  PubMed  CAS  Google Scholar 

  85. Edgington, T. S., Glassock, R. J., and Dixon, F. J. (1968) Autologous immune complex nephritis induced with renal tubular antigen. J. Exp. Med. 127, 555–572.

    Article  PubMed  CAS  Google Scholar 

  86. Ophascharoensuk, V., et al. (1998) Role of intrinsic renal cells versus infiltrating cells in glomerular crescent formation. Kidney Int. 54, 416–425.

    Article  PubMed  CAS  Google Scholar 

  87. Dworkin, L. D. and Feiner, H. D. (1986) Glomerular injury in uninephrectomized spontaneously hypertensive rats: a consequence of glomerular capillary hypertension. J. Clin. Invest. 77, 797–809.

    Article  PubMed  CAS  Google Scholar 

  88. Martinez-Maldonado, M., et al. (1987) Pathogenesis of systemic hypertension and glomerular injury in the spontaneously hypertensive rat. Am. J. Cardiol. 60, 471–521.

    Article  Google Scholar 

  89. Golbus, S. M. and Wilson, C. B. (1979) Experimental glomerulonephritis induced by in situ formation of immune complexes in glomerular capillary wall. Kidney Int. 16, 148–157.

    Article  PubMed  CAS  Google Scholar 

  90. Seiler, M. W., Venkatachalam, M. A., and Cotran, R. S. (1975) Glomerular epithelium: structural alterations induced by polycations. Science 189, 390–393.

    Article  PubMed  CAS  Google Scholar 

  91. Seiler, M. W., et al. (1977) Pathogenesis of polycation-induced alterations (“fusion”) of glomerular epithelium. Lab. Investig. 36, 48–61.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology, University of Washington Medical Center, Seattle, WA

    Raghu V. Durvasula & Stuart J. Shankland

Authors
  1. Raghu V. Durvasula
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stuart J. Shankland
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. New York Medical College, Valhalla, NY

    Michael S. Goligorsky MD, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Durvasula, R.V., Shankland, S.J. (2003). Models of Glomerulonephritis. In: Goligorsky, M.S. (eds) Renal Disease. Methods in Molecular Medicine™, vol 86. Humana Press. https://doi.org/10.1385/1-59259-392-5:47

Download citation

  • DOI: https://doi.org/10.1385/1-59259-392-5:47

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-134-9

  • Online ISBN: 978-1-59259-392-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation