Development of scarring and renal failure in a rat model of crescentic glomerulonephritis

Nephrol Dial Transplant. 1999 Jul;14(7):1658-66. doi: 10.1093/ndt/14.7.1658.


Background: The aim of this study was to develop and characterize a rat model of crescentic glomerulonephritis which progresses to glomerulosclerosis and renal failure.

Methods: Glomerulonephritis was induced in Wistar Kyoto rats by a single injection of rabbit anti-glomerular basement membrane antiserum. Albuminuria and serum creatinine were monitored. Kidneys were examined, from 2.5 h to 44 days, using light-microscopy and immunohistochemistry. To characterize the glomerular inflammatory infiltrate, glomeruli were digested to single cells and analysed by fluorescence-activated cell sorter (FACS) and by immunohistochemistry on cytospins.

Results: Rats developed albuminuria by 4 days and increased serum creatinine by day 18. Histology showed glomerular fibrinoid necrosis by day 4 and cellular crescents in a mean of 63% of glomeruli by day 11. By 6 weeks, rats had developed renal failure (mean creatinine >300 micromol/l) with 94% of the glomeruli showing glomerulosclerosis. The kidneys were also affected by severe interstitial nephritis and tubular loss. The glomeruli were infiltrated by monocytes/ macrophages (ED1+) and CD8+ (OX8+) cells. FACS analysis showed that CD8+ cells did not express T-cell markers (CD3, TCRalphabeta or TCRgammadelta) or the NK-cell marker (NKR-P1). FACS analysis of peripheral blood mononuclear cells demonstrated a population of monocytes reactive with OX8, and double-labelling of cytospin preparations of glomerular digests showed that a proportion of the CD8+ cells were a subset of ED1+ monocyte/macrophages.

Conclusions: We have characterized a reproducible model of crescentic glomerulonephritis which rapidly progresses to chronic renal failure with glomerulosclerosis and tubulo-interstitial scarring. This model will be useful for testing new therapeutic approaches in crescentic glomerulonephritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Glomerular Basement Membrane Disease / complications*
  • Anti-Glomerular Basement Membrane Disease / pathology*
  • CD8-Positive T-Lymphocytes / pathology
  • Cicatrix / etiology*
  • Cicatrix / pathology
  • Disease Models, Animal
  • Flow Cytometry
  • Male
  • Microscopy, Fluorescence
  • Nephritis, Interstitial / pathology
  • Rabbits
  • Rats
  • Rats, Inbred WKY
  • Renal Insufficiency / etiology*