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Treatment of nephrotic hyperlipoproteinemia with gemfibrozil
G C Groggel1, A K Cheung, K Ellis-Benigni
1Department of Internal Medicine, University of Utah College of Medicine, Salt Lake City.
Insights
Gemfibrozil effectively lowers cholesterol and triglycerides in nephrotic syndrome patients, reducing cardiovascular risk. Further combination therapy with colestipol enhanced these lipid improvements, though individualized treatment is still needed.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Hypercholesterolemia is a common complication of nephrotic syndrome.
- Elevated lipids in nephrotic syndrome increase cardiovascular disease risk.
- Limited safe and effective treatments were previously available.
Purpose of the Study:
- To evaluate the efficacy of gemfibrozil in managing hypercholesterolemia in nephrotic syndrome patients.
- To assess the impact of gemfibrozil, alone and in combination with colestipol, on plasma lipids and lipoproteins.
Main Methods:
- A randomized, double-blind, placebo-controlled trial was conducted.
- Eleven patients with nephrotic syndrome received gemfibrozil (600 mg twice daily) or placebo for six weeks.
- A subsequent unblinded period involved seven patients receiving gemfibrozil plus colestipol (10 grams twice daily).
Main Results:
- Gemfibrozil significantly reduced plasma triglycerides by 51% and total cholesterol by 15%.
- Low-density lipoprotein cholesterol decreased by 13%, while high-density lipoprotein cholesterol increased by 18%.
- Combined therapy further decreased total cholesterol by 26% and LDL cholesterol by 36% in remaining patients.
Conclusions:
- Gemfibrozil demonstrates efficacy in improving lipid and lipoprotein cardiovascular risk factors in nephrotic syndrome.
- Combination therapy with colestipol offers enhanced lipid-lowering effects.
- Persistent lipid elevations necessitate individualized treatment strategies.
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.