Appel G B, Appel A S
Columbia-Presbyterian Medical Center, New York, N.Y.
Am J Nephrol. 1990;10 Suppl 1:110-5. doi: 10.1159/000168204.
Hyperlipidemia is common in patients with glomerular proteinuria. It may contribute to atherosclerotic complications and accelerate glomerular damage. Early trials of the fibric acid derivative clofibrate led to a myositis syndrome causing many nephrologists to abandon attempts at treatment of nephrotic hyperlipidemia. Recent trials with lipid-lowering medications have been successful without major side effects. The bile acid sequestrants colestipol and cholestyramine bind bile acids in the gut and deplete the hepatic cholesterol pool, thus inducing LDL hepatocyte receptors. Recent studies showed a reduction of total cholesterol of 8-20% and LDL cholesterol of 19-31% without significant changes in HDL cholesterol. Probucol has reduced total cholesterol 23-30% and LDL cholesterol 23-25% in nephrotic patients. Although HDL cholesterol was reduced, the LDL/HDL ratio remains favorably changed. The fibric acid derivative gemfibrozil inhibits adipose lipolysis and enhances lipoprotein lipase activity thus decreasing LDL synthesis and increasing its removal. It caused a large decrease in triglycerides with a 13-15% decrease in total and LDL cholesterol in a recent trial. HDL cholesterol increased 18%. The HMG-CoA reductase inhibitors inhibit the rate-limiting step in cholesterol biosynthesis hence inducing an increase in LDL receptors on hepatocytes. Trials have shown decreases of 18-36% in total cholesterol and 18-47% in LDL cholesterol, while HDL cholesterol was either increased or unchanged. The use of lipid-lowering agents of several classes has been effective in ameliorating the progression of glomerular damage in a number of different models of glomerulosclerosis. Nevertheless, so far in humans lipid lowering drugs have not been established to have an effect on either the degree of proteinuria or the progression of glomerulosclerosis.
高脂血症在肾小球蛋白尿患者中很常见。它可能导致动脉粥样硬化并发症并加速肾小球损伤。早期对纤维酸衍生物氯贝丁酯的试验导致了一种肌炎综合征，使得许多肾脏病学家放弃了治疗肾病性高脂血症的尝试。最近使用降脂药物的试验取得了成功，且没有严重的副作用。胆汁酸螯合剂考来替泊和考来烯胺在肠道中结合胆汁酸，耗尽肝脏胆固醇池，从而诱导低密度脂蛋白肝细胞受体。最近的研究表明，总胆固醇降低了8 - 20%，低密度脂蛋白胆固醇降低了19 - 31%，而高密度脂蛋白胆固醇没有显著变化。普罗布考使肾病患者的总胆固醇降低了23 - 30%，低密度脂蛋白胆固醇降低了23 - 25%。虽然高密度脂蛋白胆固醇降低了，但低密度脂蛋白/高密度脂蛋白比值仍呈有利变化。纤维酸衍生物吉非贝齐抑制脂肪分解并增强脂蛋白脂肪酶活性，从而减少低密度脂蛋白合成并增加其清除。在最近的一项试验中，它使甘油三酯大幅降低，总胆固醇和低密度脂蛋白胆固醇降低了13 - 15%。高密度脂蛋白胆固醇增加了18%。HMG - CoA还原酶抑制剂抑制胆固醇生物合成中的限速步骤，从而诱导肝细胞上低密度脂蛋白受体增加。试验表明，总胆固醇降低了18 - 36%，低密度脂蛋白胆固醇降低了18 - 47%，而高密度脂蛋白胆固醇要么增加要么不变。在一些不同的肾小球硬化模型中，使用几类降脂药物有效地改善了肾小球损伤的进展。然而，到目前为止，在人类中尚未证实降脂药物对蛋白尿程度或肾小球硬化进展有影响。
