Hyperlipidemia after Renal Transplantation: Treatment with Gemfibrozil

Abstract

Thirty-eight renal allograft recipients who had persistent hyperlipidemia and stable renal function 27.8 ± 18.2 months after renal transplantation were treated with gemfibrozil. Gemfibrozil therapy resulted in a decrease in the levels of total cholesterol (TC; 297.6 ± 41.0 mg/dl to 249.2 ± 43.7 mg/dl, -16.3%; p < 0.0001), triglyceride (TG; 231.9 ± 116.8 to 125.7 ± 58.4 mg/dl, -45.8%, p < 0.0005), and LDL-cholesterol (LDL-C; 203.8 ± 37.4 to 174.5 ± 42.5 mg/dl, -14.4%; p = 0.001), which were sustained for 29.1 ± 16.0 months. Comparison of sequential lipid profiles between gemfibrozil-treated individuals and untreated hyperlipidemic controls matched for age, sex, time after transplantation, and the degree of hyperlipidemia, showed that gemfibrozil-treated patients had lower levels of TC (239.9 ± 39.5 vs. 272.8 ± 34.1 mg/dl; p < 0.005), TG (125.7 ± 67.3 vs. 167.3 ± 69.0 mg/dl; p < 0.05), and LDL-C (160.2 ± 41.3 vs. 185.3 ± 26.6 mg/dl; p < 0.05) on serial follow-up. No significant side-effect was observed with gemfibrozil therapy. Our data showed that gemfibrozil was a safe and effective drug for the treatment of hyperlipidemia in renal allograft recipients, which could reduce these patients’s long-term cardiovascular risks.

Effect of Gemfibrozil on Lipoprotein Abnormalities in Chronic Renal Insufficiency: A Controlled Study in Human Chronic Renal Disease

“…Significant reductions in plasma lipid levels were also achieved in patients without marked hyperlipidemia. The relative decreases in the levels of total cholesterol, L D L cholesterol and triglycerides were comparable to reductions of these lipid constituents re ported in previous studies of patients with chronic renal failure [9] or renal transplant patients [6] treated with gemfibrozil.…”

“…The fibrates have been shown to increase the lipoprotein lipase activity, to lower elevated serum triglycerides, to reduce the LD L cholesterol and to increase the H D L cho lesterol levels in non-renal patients [25]. Fibric acid deriv atives have also been shown to reduce plasma lipids, i.e., serum triglycerides, total cholesterol and LD L cholesterol in nephrotic patients [26,27], in patients with renal insuf ficiency [24,28,29] and in stable renal transplant patients [6,9], However, none of these studies investigated the effects of a fibrate derivative on apolipoproteins or indi vidual lipoprotein particles in predialytic renal patients.…”

“…The lipoprotein metabolism is altered in patients with nephrotic syndrome [5], in pa tients with chronic renal insufficiency [3], in patients on maintenance dialysis [3] and in post-transplant patients [6]. The clinical significance of these various forms of sec ondary dyslipoproteinemias has not been clearly estab lished [3].…”

Further Evidence of Favorable Effects of Gemfibrozil on the Lipid Profile in Renal Allograft Recipients

“…LDL-C, and HDL-C levels. In a retrospective study conducted by Chan et al [7], it was found that 300-600 mg GF/ day caused important decreases in TG, TC and LDL-C but did not induce an important increase in HDL-C. In our prospective study, significant differences were observed in all 4 parameters, probably due to the high er dose (1,200 nig/day) used without any sig nificant side effects.…”

Cardiovascular Toxicities of Immunosuppressive Agents

“…Bile acid sequestrants and nicotinic acid generally are not considered first‐line cholesterol‐lowering therapy in transplant recipients because of side‐effects and drug interactions, and gemfibrozil and probucol are not preferred because their lipid‐lowering effects are modest (31,35,73). Some investigators have reported significant reductions in total cholesterol, LDL cholesterol, and triglyceride levels in renal‐transplant recipients receiving gemfibrozil therapy (83). Fenofibrate lowered total cholesterol, LDL cholesterol, and triglyceride levels by about 20% in one study of heart‐transplant recipients, but was associated with a 67% withdrawal rate because of side‐effects (71).…”