The heterologous immune complex glomerulonephritis. A dose dependent glomerulonephritis with acute, latent and chronic phases in a long-term study.

Abstract

The pathophysiology, histology and immunohistology of acute and chronic heterologous immune complex glomerulonephritis were investigated in a long-term study in male Wistar rats. The glomerulonephritis showed 3 phases: an initial nephrotic syndrome, a latent phase with stable proteinuria (40 mg/24 h), and a terminal phase with increasing proteinuria and blood pressure, and declining serum protein concentration and creatinine clearance. Antiserum doses of 1.0, 1.5 and 2.0 ml induced maximal proteinuria (112, 257 and 272 mg/24 h respectively) after 14 days whereas normal rabbit serum and 0.5 ml antiserum gave no proteinuria. After 100 days, the rats injected with 1.0 ml of antiserum did not show physiological signs of renal disease; in the rats injected with 1.5 ml of antiserum the disease run a chronic course. Equal amounts of rabbit IgG, rat IgG and rat C3 were found in 10 glomeruli from rats 100 days after injection of 0.5, 1.0 and 2.0 ml (p greater than 0.10). Intramembranous deposits and spike formation were observed in all groups. All changes increased with greater antiserum doses. Chronically diseased animals observed from 500 to 750 days showed deposits of rabbit IgG in the basement membrane, and in most animals small amounts of rat IgG and rat C3 were also observed. This is compatible with a sustained stimulus for antibody formation throughout the course of this type of glomerulonephritis.