Direct and indirect tests of pore size and charge selectivity in nephrotic syndrome

We studied direct and indirect methods of measuring membrane charge by detecting fixed anionic sites with polyethylenimine (PEI) on the glomerular basement membrane (GEM) and Alcian blue on red blood cell (RBC) membrane (ABRBC), respectively, in 40 children with nephrotic syndrome (NS). Size selectivity of the GEM was measured indirectly by fine analysis of urinary proteins with sodium dodecyl sulfate-polyacrylamide gel electrophoresis in 22 of these children. Correlation between ABRBC and PEI was strongest (r = 0.79; p = 0.0037) in 11 children with steroid-responsive NS (SRNS), moderate (r = 0.31) in 10 children with focal glomerulosclerosis (FGS), and absent in 14 children with hepatitis B antigen membranous nephropathy (MGN) and 5 with mesangioproliferative glomerulonephritis (MPGN). ABRBC and PEI were reduced in the group as a whole as compared with their controls (ABRBC: 44.53 +/- 9.81 vs 71.54 +/- 12.14, p < 0.05; PEI: 16.31 +/- 4.34 vs 33.3 +/- 1.09, p < 0.005). This reduction was greater in SRNS (26.35 +/- 7.15 p = 0.004) but was also detected in the remainder of the group taken together (52.31 +/- 26.07, p < 0.001). Excretion of glomerular proteins was restricted by size (less than or equal to 80 kd) in SRNS but unrestricted (less than or equal to 80 kd plus > 80 kd) in FGS, MGN, and MPGN. The main cause of proteinuria is likely to be depletion of negative charge on the GEM in SRNS, and distortion of capillary pore size in MGN and MPGN, with probable overlap of these mechanisms in each disease, especially in FGS. Basement membrane injury appears widespread in SRNS but confined to the kidney in MGN and MPGN.