Immunosuppressive treatment of autologous immune complex nephritis in rats.

Abstract

Abstract Autologous immune complex nephritis was induced by intraperitoneal injections of homologous kidney extract and Freund's adjuvant in rats. The renal lesion was characterized by widening of the glomerular basement membrane and epimembranous complex deposition, and most animals manifested severe proteinuria and slowly declining glomerular filtration rates. Nine weeks after the initial injection, at a time when florid disease was present, the animals were treated with either cyclophosphamide, 6-mercaptopurine, or methylprednisolone. A fourth group of rats was not treated and served as the control. The rats receiving cyclophosphamide or 6-mercaptopurine continued to have proteinuria and their renal function deteriorated in a manner similar to the untreated animals. Additionally, they manifested a higher mortality rate than the control animals. The steroid-treated group showed equivocal results. No histologic improvement was noted in any of the treated groups. Structural and functional correlation in these studies revealed that (1) immune complex deposition frequently, but not invariably, causes proteinuria and a less striking effect on glomerular filtration rates; (2) the presence of complex deposition was associated with an increment in protein transport droplets in the proximal tubular cells suggesting enhanced reabsorption of the filtered protein. This phenomenon may have accounted for the absence of proteinuria in some of the animals with complex deposition.