Impairment of glomerular clearance of macroaggregates in immune complex glomerulonephritis

Autologous immune complex glomerulonephritis (AICGN, Heymann nephritis) in rats is characterized by the accumulation of immune deposits in a subepithelial location. Protamine-heparin aggregates with similar localization are normally cleared by glomerular epithelial cell endocytosis. The kinetics of protamine-heparin aggregate clearance from the lamina rara externa of the glomerular basement membrane in rats with AICGN were investigated. In the early stages of AICGN, the baseline numerical density of protamine-heparin aggregates at sites of immune deposit accumulation was 37.8 +/- 8.4 (mean +/- SEM) aggregates per 100 mu, significantly lower than the 71 +/- 6.9 aggregates per 100 mu in the normal appearing, immune deposit free, zone of the glomerular basement membrane (P less than 0.05). The aggregates localizing along the normal appearing parts of the lamina rara externa disappeared according to first order kinetics, similar to their clearance in normal animals. The numerical density after 3 hr in this zone of the membrane was 21.7% +/- 3.5 of the baseline at 5 min. By contrast, at sites of immune deposit accumulation, the aggregates were not cleared and actually accumulated to 160.9% +/- 12.4 of the baseline at 3 hr. It is proposed that there is impaired epithelial cell endocytic function in early AICGN, which could contribute to the perpetuation of the immune-deposit mediated lesion.