Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome

We investigated tile distribution of nephrin by immunofluorescence microsco py in renal biopsies of patients with nephrotic syndrome: 13 with membranou s glomerulonephritis (GN), 10 with minimal change GN, and seven with focal segmental glomerulosclerosis, As control, six patients with IgA GN without nephrotic syndrome and 10 normal controls were studied. We found an extensi ve loss of staining for nephrin and a shift from a podocyte-staining patter n to a granular pattern in. patients with nephrotic syndrome, irrespective of the primary disease. In membranous GN, nephrin was co-localized with IgG immune deposits. In the attempt to explain these results, we investigated in vitro whether stimuli acting on the cell cytoskeleton, known to be invol ved in the pathogenesis of GN, may induce redistribution of nephrin on the surface of human cultured podocytes, Aggregated but not disaggregated human IgG(4), plasmalemmal insertion of membrane attack complex of complement, t umor necrosis factor-alpha, and puromycin, induced the shedding of nephrin with a loss of surface expression. This phenomenon was abrogated by cytocha lasin and sodium azide, These results suggest that the activation of cell c ytoskeleton may modify surface expression of nephrin allowing a dislocation from plasma membrane to an extracellular site.