Samuelsson O, Attman P O, Knight-Gibson C, Kron B, Larsson R, Mulec H, Weiss L, Alaupovic P
Department of Nephrology, University of Göteborg, Sweden.
Nephron. 1997;75(3):286-94. doi: 10.1159/000189551.
Renal dyslipoproteinemia is characterized by the accumulation of intact and partially metabolized triglyceride-rich lipoproteins. Reduced lipolytic enzyme activities may be one of the major pathophysiological mechanisms contributing to a retarded catabolism of these lipoproteins in patients with renal insufficiency.
To evaluate the effect of gemfibrozil treatment on renal dyslipoproteinemia.
A randomized, controlled open study with 2 parallel groups.
Plasma concentrations of lipids, apolipoproteins and lipoprotein particles.
Fifty-seven non-nephrotic, non-diabetic patients with moderately advanced renal insufficiency were randomized to either treatment with gemfibrozil at dosages from 300 to 900 mg/day (n = 28) or dietary counseling (n = 29). The intervention period was 12 months. Plasma concentrations of lipids, apolipoproteins and apoA- and apoB-containing lipoprotein particles were determined at the entry and after 6 and 12 months of treatment.
No serious adverse effects occurred during the study. Six patients experienced mild gastrointestinal symptoms and prematurely withdrew from the drug treatment. In the group treated with gemfibrozil the plasma concentrations of triglycerides, total cholesterol, very low density lipoprotein (VLDL) and low density (LDL) cholesterol decreased significantly by 47, 13, 43 and 14%, respectively, in comparison to baseline. High density lipoprotein (HDL) cholesterol increased significantly by 18%. ApoB, apoC-III, apoC-III in heparin-manganese precipitate (reflecting apoC-III in VLDL and LDL) and apoE decreased significantly by 21, 18, 26 and 49%, respectively. Furthermore, gemfibrozil treatment resulted in the reduction of plasma concentrations of complex (LP-Bc) and simple (LP-B) apoB-containing lipoprotein particles by 22 and 7%, respectively. However, these changes were not statistically significant. There was a slight, insignificant increase in the levels of LP-A-I:A-II particles and no change in the levels of LP-A-I particles. In contrast to the effect of the pharmacological intervention, the dietary counseling only resulted in minor changes in the plasma lipid and apolipoprotein profiles. The only significant changes were a 10% increase in HDL cholesterol and a 35% decrease in apoE.
Gemfibrozil treatment significantly reduces both plasma lipids and apoB, apoC-III and apoE concentrations in patients with moderately advanced renal insufficiency. The results of this study indicate that gemfibrozil enhances the clearance of apoB-containing triglyceride-rich lipoproteins.
肾性血脂蛋白异常的特征是完整的和部分代谢的富含甘油三酯的脂蛋白蓄积。脂解酶活性降低可能是导致肾功能不全患者这些脂蛋白分解代谢迟缓的主要病理生理机制之一。
评估吉非贝齐治疗肾性血脂蛋白异常的效果。
一项有两个平行组的随机对照开放性研究。
血浆脂质、载脂蛋白和脂蛋白颗粒的浓度。
57例非肾病、非糖尿病的中度晚期肾功能不全患者被随机分为两组，一组接受剂量为300至900毫克/天的吉非贝齐治疗（n = 28），另一组接受饮食咨询（n = 29）。干预期为12个月。在入组时以及治疗6个月和12个月后测定血浆脂质、载脂蛋白以及含载脂蛋白A和载脂蛋白B的脂蛋白颗粒的浓度。
研究期间未发生严重不良反应。6例患者出现轻度胃肠道症状并提前退出药物治疗。与基线相比，接受吉非贝齐治疗的组中，甘油三酯、总胆固醇、极低密度脂蛋白（VLDL）和低密度脂蛋白（LDL）胆固醇的血浆浓度分别显著降低了47%、13%、43%和14%。高密度脂蛋白（HDL）胆固醇显著升高了18%。载脂蛋白B、载脂蛋白C-III、肝素-锰沉淀中的载脂蛋白C-III（反映VLDL和LDL中的载脂蛋白C-III）和载脂蛋白E分别显著降低了21%、18%、26%和49%。此外，吉非贝齐治疗使复合（LP-Bc）和简单（LP-B）含载脂蛋白B的脂蛋白颗粒的血浆浓度分别降低了22%和7%。然而，这些变化无统计学意义。LP-A-I:A-II颗粒水平有轻微的、无统计学意义的升高，LP-A-I颗粒水平无变化。与药物干预的效果相反，饮食咨询仅使血浆脂质和载脂蛋白谱有轻微变化。唯一显著的变化是HDL胆固醇升高了10%，载脂蛋白E降低了35%。
吉非贝齐治疗可显著降低中度晚期肾功能不全患者的血浆脂质以及载脂蛋白B、载脂蛋白C-III和载脂蛋白E的浓度。本研究结果表明，吉非贝齐可增强含载脂蛋白B的富含甘油三酯脂蛋白的清除。
