Lipid peroxidation in human proteinuric disease

While metabolically generated oxidants are produced locally in experimental glomerular diseases, little is still known of their significance and the respective scavenger systems in human glomerular diseases. In kidneys from patients with congenital nephrotic syndrome of the Finnish type (CNF), a human model disease of isolated proteinuria, expression of specific mRNAs for PHGPx and for mitochondrial proteins were studied. PHGPx and the mitochondrially encoded subunits of cytochrome c oxidase were distinctly down-regulated within the glomeruli of CNF kidneys. Increases of lipidperoxidation products MDA and 4-HNE were constantly found in the glomeruli of CNF. These findings suggest that local mitochondrial damage initiate LPO, which then causes deposition of the cytotoxic LPO products in glomeruli, as seen especially in CNF kidneys. Together with down-regulation of the local antioxidant protection, these may be important pathophysiologic mechanisms in human glomerular disease.