Studies of progressive glomerular sclerosis in the rat

To obtain a better understanding of the sequential development of sclerosis in immune glomerular disease, the authors induced experimental membranous nephropathy in unilaterally nephrectomized rats and evaluated the lesions that developed over a 35-week period. Serial renal biopsies were examined by light and immunofluorescence microscopy for IgG, C3, neoantigens of the membrane attack complex (MAC), and interstitial (Type III) and basement membrane (Type IV) collagen. Urinary protein excretion increased from 208 +/- 19 mg/day to 308 +/- 36 mg/day during the period of observation. Progressive mesangial sclerosis, crescent formation, and interstitial fibrosis developed in association with deposition of Type IV but not Type III collagen in the glomeruli. Capillary wall deposits of IgG, C3, and MAC gradually decreased, whereas coarse granular deposits of C3 and MAC were visible in sclerotic areas beginning at 8 weeks. The appearance of complement components in early sclerotic lesions raises the possibility that they are of pathogenetic importance. The absence of interstitial collagen in sclerotic glomeruli suggests that the components of the lesion are produced solely by glomerular cells.