A highly cationic protein in plasma and urine of children with steroid-responsive nephrotic syndrome

We postulated that the reduction of surface negative charge on the glomerular capillary wall, which is believed to underlie the proteinuria of steroid-responsive nephrotic syndrome (SRNS), might be due to the presence of a cationic substance which binds to and neutralizes the negative charge on cells and membranes. Using a method to detect charge neutralizing substances based on inhibition of binding of the cationic dye Alcian blue 8GX to heparin, plasma and urine from children with SRNS were found to contain a protease-sensitive charge-neutralizing factor, which was not present in plasma or urine of healthy individuals. This factor has been partially purified from SRNS plasma and urine by ion exchange chromatography on QAE Sephadex, gel filtration on Sephadex G150, and FPLC on Mono-S. This cationic protein, which binds to and neutralizes the charge on heparin, may also neutralize the negative charge on the glomerular capillary wall and may thus be involved in the pathogenesis of SRNS.