Glomerular anionic sites in minimal change nephrotic syndrome and focal segmental glomerulosclerosis

In order to examine the changes in charge of the glomerular basement membrane (GBM) in nephrotic syndrome, anionic sites in the GBM were studied quantitatively. Renal biopsy specimens were obtained from 5 children with minimal change nephrotic syndrome (MCNS) and 5 with nephrotic syndrome and focal segmental glomerulosclerosis (FSGS). Biopsy specimens obtained from 5 patients without proteinuria were also examined as controls. Anionic sites were stained with polyethyleneimine (PEI) as a cationic probe and were examined by electron microscopy. The number of PEI-labeled anionic sites in the lamina rara externa of the GBM was counted in the glomerular capillary region and in the paramesangial region separately. The number of anionic sites per 1000-nm GBM was 20.9 +/- 0.6 in the capillary and 21.2 +/- 0.7 in the paramesangium in controls. They were significantly decreased in MCNS (16.5 +/- 0.7 in the capillary and 16.9 +/- 0.5 in the paramesangium, p < 0.001) and in FSGS (16.7 +/- 0.7 in the capillary and 17.0 +/- 0.6 in the paramesangium, p < 0.001). The decrease of anionic sites suggests a defect in the charge-selective barrier in the lamina rara externa of the GBM in MCNS and FSGS, and this defect both in the capillary and in the paramesangium may be responsible for the proteinuria in these two conditions.