Treatment of nephrotic hyperlipoproteinemia with gemfibrozil

Abstract

Hypercholesterolemia is a known complication of the nephrotic syndrome. Patients with persistent proteinuria and prolonged hypercholesterolemia are probably at increased risk for cardiovascular disease. Until recently there has been no safe and effective treatment for this disorder. The effects of gemfibrozil on plasma lipids and lipoproteins in hypercholesterolemic patients with the nephrotic syndrome were therefore studied. Eleven patients with the nephrotic syndrome were studied in a randomized, double-blind placebo-controlled trial with six-week treatment periods. Gemfibrozil 600 mg or placebo was administered twice a day. There was a third unblinded period in which seven patients received gemfibrozil plus the bile acid-binding resin, colestipol, 10 grams twice a day. Gemfibrozil treatment produced a marked reduction in plasma triglyceride (51%, P = 0.001) and a 15% decrease in plasma total cholesterol (P = 0.003). Low density lipoprotein cholesterol decreased 13% (P greater than 0.05), high density lipoprotein cholesterol increased 18% (P = 0.006) and the ratio of low density lipoprotein to high density lipoprotein cholesterol fell 26% (P = 0.01). Apolipoprotein A-l was unchanged while apolipoprotein B decreased 26% (P = 0.006). Four patients were unable to complete period 3 because of gastrointestinal symptoms. The remaining patients had further improvement in plasma lipids and lipoproteins with the combined therapy: total cholesterol further decreased 26%, triglycerides decreased 17%, low-density lipoprotein cholesterol decreased 36%, high-density lipoprotein to high-density lipoprotein cholesterol fell 33%. Gemfibrozil improved lipid and lipoprotein cardiovascular risk factors without major toxicity. Persistent elevations in total plasma and low-density lipoprotein cholesterol during gemfibrozil treatment, however, indicate the need for individualized drug therapy.