Ultrastructural alteration of glomerular anionic sites in nephrotic patients

The relationship of glomerular anionic sites to proteinuria was examined ultrastructurally in human nephrotic syndrome. The anionic sites were analysed morphometrically in patients with minimal-change nephrotic syndrome (MCNS, 11 patients) and in other glomerulonephritides complicated with nephrotic syndrome (4 patients) by the high-iron diamine-thiocarbohydrazide-silver proteinate method. The anionic sites in MCNS patients in remission (7 patients) were normal. In contrast, the anionic sites in nephrotic patients with MCNS (4 patients) and the other glomerulonephritides were decreased in number. Moreover, smaller and irregularly distributed anionic sites or the greater loss of them from the paramesangial region were observed in the nephrotic patients. The loss of glomerular anionic sites may induce structural alteration of the glomerular basement membrane and mesangial matrix. The loss and structural abnormalities of glomerular anionic sites in nephrotic patients may be one of the mechanisms responsible for massive proteinuria.