Glomerular epithelial abnormalities associated with the onset of proteinuria in aminonucleoside nephrosis

A sequential ultrastructural study has been made of glomerular podocytic epithelium before and after the onset of proteinuria induced by daily subcutaneous injections of low doses of puromycin aminonucleoside (PAN). At 4 days, before the onset of proteinuria, the principal change was extensive replacement of podocytic foot processes by broad expanses of epithelial cytoplasm. At 5 days, when proteinuria had developed, the epithelial cells showed in addition multiple cytoplasmic droplets, many large balloon like vacuoles, some of which were ruptured, and many foci of epithelial detachment from the glomerular basement membrane (GBM). Of particular significance, the onset of proteinuria coincided precisely with the development of areas of epithelial detachment that led to direct continuity between externally denuded GBM and the urinary space. It seems likely that these areas are the primary sites of protein leakage across the GBM in this experimental model.