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

Background. The aim of this study was to develop and characterize a rat mod el of crescentic glomerulonephritis which progresses to glomerulosclerosis and renal failure. Methods. Glomerulonephritis was induced in Wistar Kyoto rats by a single in jection of rabbit antiglomerular basement membrane antiserum. Albuminuria a nd 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 cell s and analysed by fluorescence-activated cell sorter (FACS) and by immunohi stochemistry on cytospins. Results. Rats developed albuminuria by 4 days and increased serum creatinin e by day 18. Histology showed glomerular fibrinoid necrosis by day 4 and ce llular crescents in a mean of 63% of glomeruli by day 11. By 6 weeks, rats had developed renal failure (mean creatinine > 300 mu mol/l) with 94% of th e glomeruli showing glomerulosclerosis. The kidneys were also affected by s evere interstitial nephritis and tubular loss. The glomeruli were infiltrat ed by monocytes/ macrophages (ED1+) and CD8+ (OX8+) cells. FACS analysis sh owed that CD8+ cells did not express T-cell markers (CD3, TCR alpha beta or TCR gamma delta) or the NK-cell marker (NKR-P1). FACS analysis of peripher al blood mononuclear cells demonstrated a population of monocytes reactive with OX8, and double-labelling of cytospin preparations of glomerular diges ts showed that a proportion of the CD8+ cells were a subset of ED1+ monocyt e/macrophages. Conclusions. We have characterized a reproducible model of crescentic glome rulonephritis which rapidly progresses to chronic renal failure with glomer ulosclerosis and tubulo-interstitial scarring. This model will be useful fo r testing new therapeutic approaches in crescentic glomerulonephritis.