Analysis of Renal Fibrosis in a Rabbit Model of Crescentic Nephritis

The pathogenesis of renal fibrosis in crescentic nephritis is incompletely understood. To improve our understanding of this process, crescentic neiphritis was induced in New Zealund White rabbits by administration of guinea pig antiglomerular basement membrane IgG after sensitization with guinea pig IgG; and their kidneys were analyzed for the development of fibrosis. Collagensynthesis in renal cortical tissue was signifi-cantly.elevated by day 3, peaked at days 7-15, and returned towards baseline by day 21. Collagen content of both glomeruli and cortex were increased starting on days 14-16, and re-mained constant in cortex thereafter. Light microscopic analy-sis wasMuch less sensitive, revealing fibrosis only after day 21. Immunofluorescence.revealed that type IV collagen was dis-tributqd primarily in the glomerulus, while types I and III were increased in the, glomerulus and interstitium. Thus, in this model of crescentic nephritis, fibrosis, as assessed biochemi-cally, developed early at time points when. morphologic analy-sis failed to detect such a development. Hence early therapeu-tic intervention, before morphologic evidence of fibrosis is evi-dent, may be more successful in arresting the progression of this disease before it reaches irreversible terminal stages