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 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.
Tam
F W
FW
Division of Medicine and Department of Histopathology, Imperial College School of Medicine, Hammersmith Hospital, London, UK. ftam@rpms.ac.uk
Smith
J
J
Morel
D
D
Karkar
A M
AM
Thompson
E M
EM
Cook
H T
HT
Pusey
C D
CD
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000150:complications* / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002921:Cicatrix / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D008297:Male; D008856:Microscopy, Fluorescence; D009395:Nephritis, Interstitial / Q000473:pathology; D011817:Rabbits; D051381:Rats; D011921:Rats, Inbred WKY; D051437:Renal Insufficiency / Q000209:etiology*