Background. While metabolically generated oxidants are produced locally in
experimental glomerular diseases, little is still known of their significan
ce and the respective scavenger systems in human glomerular diseases.
Methods. Here we studied kidneys from patients with congenital nephrotic sy
ndrome of the Finnish type (CNF). a human model disease of isolated protein
uria. Expression of specific mRNAs for a major antioxidant system against l
ipoperoxidation [phospholipid hydroperoxide glutathione peroxidase (PHGPx)]
and for mitochondrial proteins were studied in Northern blotting together
with analysis of PHGPx in semi-quantitative reverse transcription-polymeras
e chain reaction (RT-PCR). The respective proteins and lipoperoxide (LPO) a
dducts malonyldialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were analyzed i
n immunohistochemistry.
Results. PHGPx and the mitochondrially encoded subunits of cytochrome-c-oxi
dase were distinctly down-regulated within the glomeruli of CNF kidneys. Th
ese changes were confirmed in semiquantitative RT-PCR. Increases of lipoper
oxidation products MDA and 4-HNE were constantly found in the glomeruli of
CNF. In agreement with findings in CNF. similar results were obtained in bi
opsies from other human glomerular diseases.
Conclusions. These findings suggest that local mitochondrial damage initiat
es LPO. which then causes deposition of the cytotoxic LPO products in glome
ruli, as seen especially in CNF kidneys. Together with down-regulation of t
he local antioxidant protection, these may be important pathophysiologic me
chanisms in human glomerular disease.