Watorek E, Szymczak M, Boratynska M, Patrzalek D, Klinger M
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
Transplant Proc. 2011 Oct;43(8):2967-9. doi: 10.1016/j.transproceed.2011.08.009.
Cardiovascular diseases (CVD) are the leading cause of mortality in renal transplant recipients. Various traditional and unconventional cardiovascular risk factors are potentiated by the adverse effects of immunosuppressive drugs. The mammalian target of rapamycin (mTOR) inhibitors have shown cardioprotective effects in experimental studies, but their influence on CVD in renal transplantation is unclear. The study included 115 kidney transplant recipients treated with mTOR inhibitors with steroids. A group of 38 patients received additionally small doses of calcineurin inhibitor. The control group consisted of 58 kidney transplant recipients randomly chosen among the population of patients transplanted at the same time, who received a calcineurin inhibitor, mycophenolate mofetil or sodium plus steroids. No differences in age, gender, duration of pretransplantat dialysis, time after transplantation, body mass index or glycated hemoglobin existed between the groups. Blood pressure and number of antihypertensive agents, high-density lipoprotein cholesterol, and uric acid levels were similar. The prevalence of diabetic, ischemic, or hypertensive nephropathy as the reason for end-stage renal disease was similar (P=.08). The study group showed higher mean values of total cholesterol (249 vs 204.6 mg/dL; P<.0001) and low-density lipoprotein 136.5 vs 117.7 mg/dL; (P=.015), as well as median values of triglycerides (202 vs 142 mg/dL; P<.0001) and proteinuria (P=.0002). mean estimated glomerular filtration rate was lower in the study group (42.9 vs 51.9 mL/min; P=.0003). Posttransplant diabetes appeared in 38% of the study group compared to 20% of the controls (P=.08). The incidence of coronary artery disease was higher among patients treated with mTOR inhibitors (P=.04). CVD, defined as myocardial infarction, percutaneous coronary intervention, stroke, aortic aneurysm, pulmonary thromboembolism, sudden cardiac death appeared in 26 study group compared with four control patients (P=.24). The risk of any CVD was not significantly higher among patients receiving mTOR inhibitors hazard ratio 1.94; 95% confidence interval 0.83-4.52). In conclusion, no correlation was observed between the duration of mTOR therapy and CVD.
心血管疾病（CVD）是肾移植受者死亡的主要原因。免疫抑制药物的不良反应会增强各种传统和非传统的心血管危险因素。雷帕霉素靶蛋白（mTOR）抑制剂在实验研究中已显示出心脏保护作用，但其对肾移植中CVD的影响尚不清楚。该研究纳入了115例接受mTOR抑制剂和类固醇治疗的肾移植受者。一组38例患者额外接受小剂量钙调神经磷酸酶抑制剂治疗。对照组由58例肾移植受者组成，他们是从同时进行移植的患者群体中随机选取的，接受钙调神经磷酸酶抑制剂、霉酚酸酯或硫唑嘌呤加类固醇治疗。两组在年龄、性别、移植前透析时间、移植后时间、体重指数或糖化血红蛋白方面无差异。血压、抗高血压药物数量、高密度脂蛋白胆固醇和尿酸水平相似。作为终末期肾病病因的糖尿病、缺血性或高血压肾病的患病率相似（P = 0.08）。研究组的总胆固醇（249 vs 204.6 mg/dL；P < 0.0001）、低密度脂蛋白（136.5 vs 117.7 mg/dL；P = 0.015）、甘油三酯中位数（202 vs 142 mg/dL；P < 0.0001）和蛋白尿（P = 0.0002）的平均值较高。研究组的平均估计肾小球滤过率较低（42.9 vs 51.9 mL/min；P = 0.0003）。研究组中38%出现移植后糖尿病，而对照组为20%（P = 0.08）。接受mTOR抑制剂治疗的患者中冠状动脉疾病的发生率较高（P = 0.04）。定义为心肌梗死、经皮冠状动脉介入治疗、中风、主动脉瘤、肺血栓栓塞、心源性猝死的CVD在研究组中有26例，而对照组有4例（P = 0.24）。接受mTOR抑制剂治疗的患者发生任何CVD的风险没有显著更高（风险比1.94；95%置信区间0.83 - 4.52）。总之，未观察到mTOR治疗持续时间与CVD之间存在相关性。
