Glomerular and urinary heparan sulphate in congenital nephrotic syndrome

Studies using cationic probes have suggested that a reduction in glomerular anionic sites, composed principally of the glycosaminoglycan heparan sulphate, is responsible for the abnormal glomerular permeability in the congenital nephrotic syndrome (CNS). We therefore analysed the glycosaminoglycan content of the glomerular basement membrane (GBM) from an infant who died of CNS and from an infant who died of unrelated causes. We also measured the urinary excretion of glycosaminoglycans in children with nephrotic syndrome, both congenital and acquired, and in healthy children. Heparan sulphate constituted 59% of the glycosaminoglycan content of the GBM in the normal infant, the other principal glycosaminoglycan being chondroitin sulphate. In the GBM from the infant with CNS the heparan sulphate was greatly reduced, constituting only 3% of total glycosaminoglycans. The urinary excretion of heparan sulphate was significantly increased in CNS (expressed both in relation to creatinine and to chondroitin sulphate) compared with normal children and to those with acquired nephrotic syndrome. Diminished GBM content of heparan sulphate may be responsible for the abnormal glomerular permeability in CNS and may be a consequence of defective incorporation of heparan sulphate into the GBM with subsequent loss into the urine.