Sequential ultrastructural podocytic lesions and development of proteinuria in serum sickness nephritis in the rat

Abstract

Serum sickness nephritis was induced in Fisher rats by immunization with egg albumin (EA) and correlations between immune complex deposition, alterations of podocytes and development of proteinuria were analysed. Immunoelectron microscopy showed that EA, rat IgG and C3 were confined to the electron-dense deposits (Ds). From 3 weeks, when significant proteinuria had developed, the subepithelial region was filled with large numbers of Ds on the peripheral capillary wall as well as in the paramesangium. The loss of slit diaphragms and detachment of foot processes overlying Ds were observed and the escape of Ds into urinary space was frequently detected. Morphometric evaluation showed that the volume of subepithelial Ds and the number of the sites of podocytic detachment correlate significantly with the amount of proteinuria. In addition, the native ferritin injected via the abdominal aorta was seen in large amounts in the urinary space near the areas devoid of epithelial covering. The development of podocytic detachment was clearly coincident with the appearance of proteins with a larger molecular weight in urine. From these results, it is suggested that the loss of slit diaphragms and the detachment of podocytes resulting from the progressive accumulation of Ds will allow the leakage of proteins of larger molecular weight across the capillary wall. These podocytic lesions may be one of the main aetiologies for the development of heavy proteinuria in this model.