Immune complex acute necrotizing glomerulonephritis with progression to diffuse glomerulosclerosis. A murine model

Male BALB/c mice given daily intraperitoneal injections of 4 mg of horse-spleen apoferritin develop, in the majority of cases, a proliferative and necrotizing glomerulonephritis with leukocytic infiltration and extensive intraglomerular thrombosis within 10 to 14 days, as previously reported. We now show that if injection of the antigen is discontinued, surviving animals develop extensive glomerulosclerosis (GS). Ten of 13 mice treated as indicated above and sacrificed 4 months after the last horse-spleen apoferritin injection developed segmental GS involving over 40% of their glomeruli. Tubulointerstitial damage of proportionate severity also developed. Ultrastructurally, pronounced mesangial expansion due to matrix deposition obliterated the glomerular architecture. We offer this as a reproducible model of immune complex-mediated GS particularly suited to the study of cellular interactions involved in the pathogenesis of GS.