Kasiske B L, Heim-Duthoy K L, Singer G G, Watschinger B, Germain M J, Bastani B
Department of Medicine, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN 55415, USA.
Transplantation. 2001 Jul 27;72(2):223-7. doi: 10.1097/00007890-200107270-00009.
Preliminary results from clinical trials suggest that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors may help prevent acute renal allograft rejection. However, the mechanism for this putative effect of 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors, and whether it is independent of lipid-lowering per SE are unknown.
Immediately after renal transplantation we randomly allocated (proportioned 2:1:2) patients to: 1) simvastatin (10 mg/day, n=53), 2) simvastatin placebo plus gemfibrozil (dose adjusted for renal function, n=36), and 3) simvastatin placebo (n=52).
Simvastatin, but not gemfibrozil, reduced total and low density lipoprotein cholesterol during the first 90 days posttransplant. There were no major adverse effects of therapy. However, there were no effects of treatment on acute rejection. Indeed, survival free of acute rejection at 90 days was 72% in the simvastatin group, 72% in the gemfibrozil group, and 77% in the placebo control group (P=0.771). A post hoc power analysis suggested that there was only a 7.5% chance that a true effect of simvastatin on acute rejection (versus placebo) was not detected, and a 2.5% chance that an effect of gemfibrozil on acute rejection (versus placebo) was not detected in this study.
Lipid-lowering agents may not reduce the incidence of acute renal allograft rejection. However, additional studies are needed to confirm this observation. In the mean time, many if not most renal transplant recipients should be treated with HMG-CoA reductase inhibitors starting early posttransplant to prevent cardiovascular disease complications. The results of this study suggest that starting lipid-lowering therapy immediately after renal transplantation is both safe and effective in lowering total and low density lipoprotein cholesterol.
临床试验的初步结果表明，3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂可能有助于预防急性肾移植排斥反应。然而，3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂这种假定作用的机制，以及它是否独立于降血脂作用本身尚不清楚。
肾移植术后，我们立即将患者随机分配（比例为2:1:2）至：1）辛伐他汀组（10毫克/天，n = 53），2）辛伐他汀安慰剂加吉非贝齐组（剂量根据肾功能调整，n = 36），3）辛伐他汀安慰剂组（n = 52）。
辛伐他汀可降低移植后前90天的总胆固醇和低密度脂蛋白胆固醇，但吉非贝齐无此作用。治疗无重大不良反应。然而，治疗对急性排斥反应无影响。实际上，辛伐他汀组90天时无急性排斥反应的生存率为72%，吉非贝齐组为72%，安慰剂对照组为77%（P = 0.771）。事后效能分析表明，本研究中未检测到辛伐他汀对急性排斥反应（与安慰剂相比）的真实效应的可能性仅为7.5%，未检测到吉非贝齐对急性排斥反应（与安慰剂相比）的效应的可能性为2.5%。
降脂药物可能不会降低急性肾移植排斥反应的发生率。然而，需要更多研究来证实这一观察结果。同时，许多（如果不是大多数）肾移植受者应在移植后早期开始接受HMG-CoA还原酶抑制剂治疗，以预防心血管疾病并发症。本研究结果表明，肾移植后立即开始降脂治疗在降低总胆固醇和低密度脂蛋白胆固醇方面既安全又有效。
