Progressive glomerular sclerosis in experimental antiglomerular basement membrane glomerulonephritis

Abstract

A model of chronic progressive glomerular sclerosis in experimental antiglomerular basement membrane (anti-GBM) glomerulonephritis was developed in Wistar rats. Wistar rats given the accelerated form of anti-GBM anti-body glomerulonephritis initially developed significant proteinuria and renal insufficiency associated primarily with a decrease in glomerular filtration rate (GFR) with normal renal clearance of para-aminohippuric acid and with markedly reduced filtration fraction. The glomerular functional abnormalities were associated with marked glomerular hypercellularity due to leukocytic infiltration as well as proliferation of intrinsic glomerular cells with crescent formation. Late in the course of the disease, by day 21, GFR had fallen further, associated with a parallel decrease in the clearance of para-aminohippuric acid and a normal filtration fraction. At this stage, glomerular hypercellularity had diminished and was replaced by glomerular sclerosis. The model appears to be a reproducible form of chronic glomerulosclerosis and demonstrates that the chronic phase of glomerular basement membrane (GBM) glomerulonephritis is distinctly different from that of the acute phase. It provides a controllable setting to study the glomerular sclerotic process independent of the initial inflammatory changes.