Cholestyramine resin ameliorates chronic aminonucleoside nephrosis

We chose to assess the role of cholesterol reduction in chronic aminonucleoside nephrosis by pharmacologically lowering serum cholesterol with cholestyramine. Two groups of rats were made nephrotic with a single intravenous dose of puromycin aminonucleoside (PA): one group (PA/resin) received 5% (w:w in diet) cholestyramine resin and the dietary control group (PA/cell) received 5% cellulose. Cholestyramine-treated rats demonstrated significant functional and histological protection. Recurrent proteinuria was significantly lower in PA/resin animals. Whole-kidney glomerular filtration rate in the PA/resin group was preserved at a level equivalent to normal age-matched control rats whereas the PA/cell group had a significantly lower value than did the normal animals. The extent of segmental glomerulosclerosis 24 wk after PA delivery was significantly lower in the PA/resin group. These results suggest a role for hyperlipidemia as one of the mechanisms involved in the pathogenesis of progressive glomerular disease.