EFFECT OF GEMFIBROZIL ON LIPOPROTEIN ABNORMALITIES IN CHRONIC RENAL-INSUFFICIENCY - A CONTROLLED-STUDY IN HUMAN CHRONIC RENAL-DISEASE

Background: Renal dyslipoproteinemia is characterized by the accumulat ion of intact and partially metabolized triglyceride-rich lipoproteins . Reduced lipolytic enzyme activities may be one of the major pathophy siological mechanisms contributing to a retarded catabolism of these l ipoproteins in patients with renal insufficiency. Objective: To evalua te the effect of gemfibrozil treatment on renal dyslipoproteinemia. St udy design: A randomized, controlled open study with 2 parallel groups . Outcome variables: Plasma concentrations of lipids, apolipoproteins and lipoprotein particles. Patients and methods: Fifty-seven non-nephr otic, non-diabetic patients with moderately advanced renal insufficien cy were randomized to either treatment with gemfibrozil at dosages fro m 300 to 900 mg/day (n = 28) or dietary counseling (n = 29). The inter vention period was 12 months. Plasma concentrations of lipids, apolipo proteins and apoA- and apoB-containing lipoprotein particles were dete rmined at the entry and after 6 and 12 months of treatment. Results: N o serious adverse effects occurred during the study. Six patients expe rienced mild gastrointestinal symptoms and prematurely withdrew from t he drug treatment. In the group treated with gemfibrozil the plasma co ncentrations of triglycerides, total cholesterol, very low density lip oprotein (VLDL) and low density (LDL) cholesterol decreased significan tly by 47, 13, 43 and 14%, respectively, in comparison to baseline. Hi gh density lipoprotein (HDL) cholesterol increased significantly by 18 %. ApoB, apoC-III, apoC-III in heparin-manganese precipitate (reflecti ng apoC-III in VLDL and LDL) and apoE decreased significantly by 21, 1 8, 26 and 49%, respectively. Furthermore, gemfibrozil treatment result ed in the reduction of plasma concentrations of complex (LP-Bc) and si mple (LP-B) apoB-containing lipoprotein particles by 22 and 7%, respec tively. However, these changes were not statistically significant. The re was a slight, insignificant increase in the levels of LP-A-I:A-II p articles and no change in the levels of LP-A-I particles. In contrast to the effect of the pharmacological intervention, the dietary counsel ing only resulted in minor changes in the plasma lipid and apolipoprot ein profiles. The only significant changes were a 10% increase in HDL cholesterol and a 35% decrease in apoE. Conclusions: Gemfibrozil treat ment significantly reduces both plasma lipids and apoB, apoC-III and a poE concentrations in patients with moderately advanced renal insuffic iency. The results of this study indicate that gemfibrozil enhances th e clearance of apoB-containing triglyceride-rich lipoproteins.