An Ultrastructural Study of Glomerular Permeability in Aminonucleoside Nephrosis Using Catalase as a Tracer Protein*,~/ By

Physiological studies (1-4) have indicated that increased glomerular permeability is the major cause of proteinuria in human and experimental nephrosis, but the ultrastructural basis for such protein leakage is poorly understood. Previous morphological studies using ferritin (tool wt 500,000) (5, 6) have shown that the glomerular basement membrane becomes more permeable to this particle in experimental nephrosis induced by the aminonucleoside of puromycin (7), and it has been suggested that a basement membrane lesion is the primary cause of proteinuria (6). However, the most striking ultrastructural changes in experimental aminonucleoside nephrosis and human lipoid nephrosis occur not in the basement membrane but in the epithelial cells of the glomerulus. These epithelial alterations, which include fusion of foot processes and vacuolization, have been considered to be secondary to the proteinuria (6). In a previous communication (8) we have reviewed these changes and reported that the enzyme tracer horseradish peroxidase (HRP) (tool wt 40,000) is transported across altered epithelial cells into the urinary space through a system of vacuoles. The contribution of such a vacuolar pathway to the pathogenesis of proteinuria could not be clearly assessed from the peroxidase experiments since this enzyme also diffused easily through normal basement membranes and along intercellular junctions of fused epithelial cells in nephrotic glomeruli. We report here on the passage of beef liver catalase across the glomerular capillary wall into the urinary space in aminonucleoside nephrosis. This enzyme,