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.
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.
Authors: Jacques Behmoaras; Jennifer Smith; Zelpha D'Souza; Gurjeet Bhangal; Ratana Chawanasuntoropoj; Frederick W K Tam; Charles D Pusey; Timothy J Aitman; H Terence Cook Journal: J Am Soc Nephrol Date: 2010-05-20 Impact factor: 10.121
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Authors: Tabitha Turner-Stokes; Ana Garcia Diaz; Damilola Pinheiro; Maria Prendecki; Stephen P McAdoo; Candice Roufosse; H Terence Cook; Charles D Pusey; Kevin J Woollard Journal: J Am Soc Nephrol Date: 2020-08-31 Impact factor: 10.121
Authors: Jennifer Smith; John P McDaid; Gurjeet Bhangal; Ratana Chawanasuntorapoj; Esteban S Masuda; H Terence Cook; Charles D Pusey; Frederick W K Tam Journal: J Am Soc Nephrol Date: 2009-12-03 Impact factor: 10.121
Authors: Michael Schroeter; Guido Stoll; Robert Weissert; Hans-Peter Hartung; Hans Lassmann; Sebastian Jander Journal: Am J Pathol Date: 2003-10 Impact factor: 4.307
Authors: H Terence Cook; Sarah B Khan; Andrew Allen; Gurjeet Bhangal; Jennifer Smith; Roy R Lobb; Charles D Pusey Journal: Am J Pathol Date: 2002-10 Impact factor: 4.307