Nephrology Dialysis Transplantation, Vol 14, Issue 7 1658-1666, Copyright © 1999 by Oxford University Press
F Tam, J Smith, D Morel, A Karkar, E Thompson, H Cook and C Pusey
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 antiglomerular 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 &mgr;mol/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,
TCR&agr;{beta} or TCR&ggr;&dgr;) or the NK-cell marker
(NKR-01). 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. Key words: crescentic;
glomerular basement membrane; glomerulonephritis; nephrotoxic nephritis;
Wistar Kyoto rat
ORIGINAL ARTICLES
Development of scarring and renal failure in a rat model of crescentic glomerulonephritis
Renal Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK; Corresponding author e-mail: ftam@rpms.ac.uk
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