Thomas M E, Harris K P, Ramaswamy C, Hattersley J M, Wheeler D C, Varghese Z, Williams J D, Walls J, Moorhead J F
Department of Nephrology, Royal Free Hospital, London, United Kingdom.
Kidney Int. 1993 Nov;44(5):1124-9. doi: 10.1038/ki.1993.358.
Experimental evidence suggests that lipid lowering therapy could slow the progression of renal disease in humans. We have conducted a double-blind, placebo controlled trial of the HMG CoA reductase inhibitor simvastatin in patients with the nephrotic syndrome or significant proteinuria (> 1 g/day) and hypercholesterolemia (> or = 6.5 mmol/liter). Patients were placed on a lipid lowering diet for at least 10 weeks before randomization. After a four-week placebo run-in, 30 adults were randomized to simvastatin or placebo therapy (10 mg/day, increasing to 20 to 40 mg/day as required) for 24 weeks. There were seven dropouts, none of whom were "definitely" related to drug therapy. Total and LDL cholesterol levels fell by a mean of 33 and 31%, respectively, in simvastatin treated patients, compared with only 5 and 1% in patients on placebo (P < 0.001, P = 0.002, respectively). Apolipoprotein B100 levels fell by a mean of 31% in the simvastatin group but rose 0.3% in the placebo group (P = 0.014). There were no significant changes in HDL levels. There were no significant differences between the groups in their urine protein levels, their rise in plasma creatinine, or decline in plasma inulin clearance. Simvastatin is a safe, effective therapy for hypercholesterolemia in proteinuric states. A much larger trial is needed to show if potent lipid-lowering therapy slows progression of hypercholesterolemic proteinuric diseases.
实验证据表明，降脂治疗可能会减缓人类肾脏疾病的进展。我们对患有肾病综合征或显著蛋白尿（>1克/天）且高胆固醇血症（>或=6.5毫摩尔/升）的患者进行了一项关于HMG CoA还原酶抑制剂辛伐他汀的双盲、安慰剂对照试验。在随机分组前，患者接受至少10周的降脂饮食。经过为期四周的安慰剂导入期后，30名成年人被随机分为辛伐他汀组或安慰剂组，接受24周治疗（10毫克/天，根据需要增至20至40毫克/天）。有7名患者退出试验，其中无一例“肯定”与药物治疗有关。辛伐他汀治疗组患者的总胆固醇和低密度脂蛋白胆固醇水平分别平均下降了33%和31%，而安慰剂组患者仅分别下降了5%和1%（分别为P<0.001，P = 0.002）。辛伐他汀组载脂蛋白B100水平平均下降31%，而安慰剂组上升0.3%（P = 0.014）。高密度脂蛋白水平无显著变化。两组在尿蛋白水平、血浆肌酐升高或血浆菊粉清除率下降方面无显著差异。辛伐他汀是治疗蛋白尿状态下高胆固醇血症的一种安全、有效的疗法。需要进行更大规模的试验来证明强效降脂治疗是否能减缓高胆固醇血症性蛋白尿疾病的进展。
