Department of Pharmacology, Rouen University Hospital, University of Rouen, Rouen, France.
Am J Transplant. 2011 Nov;11(11):2414-22. doi: 10.1111/j.1600-6143.2011.03697.x. Epub 2011 Sep 19.
Whether or not a cyclosporine A (CsA)-free immunosuppressant regimen based on sirolimus (SRL) prevents aortic stiffening and improves central hemodynamics in renal recipients remains unknown. Forty-four patients (48 ± 2 years) enrolled in the CONCEPT trial were randomized at week 12 (W12) to continue CsA or switch to SRL, both associated with mycophenolate mofetil. Carotid systolic blood pressure (cSBP), pulse pressure (cPP), central pressure wave reflection (augmentation index, AIx) and carotid-to-femoral pulse-wave velocity (PWV: aortic stiffness) were blindly assessed at W12, W26 and W52 together with plasma endothelin-1 (ET-1), thiobarbituric acid-reactive substances (TBARS) and superoxide dismutase (SOD) and catalase erythrocyte activities. At W12, there was no difference between groups. At follow-up, PWV, cSBP, cPP and AIx were lower in the SRL group. The difference in PWV remained significant after adjustment for blood pressure and eGFR. In parallel, ET-1 decreased in the SRL group, while TBARS, SOD and catalase erythrocyte activities increased in both groups but to a lesser extent in the SRL group. Our results demonstrate that a CsA-free regimen based on SRL reduces aortic stiffness, plasma endothelin-1 and oxidative stress in renal recipients suggesting a protective effect on the arterial wall that may be translated into cardiovascular risk reduction.
基于西罗莫司(SRL)的环孢素 A(CsA)免费免疫抑制方案是否能预防肾移植受者的主动脉僵硬并改善中心血液动力学尚不清楚。CONCEPT 试验共纳入 44 名患者(48±2 岁),他们在第 12 周(W12)随机分为继续使用 CsA 或转换为 SRL 组,两组均联合使用霉酚酸酯。在 W12、W26 和 W52 时,通过盲法评估颈动脉收缩压(cSBP)、脉压(cPP)、中心压力波反射(增强指数,AIx)和颈股脉搏波速度(PWV:主动脉僵硬),同时检测血浆内皮素-1(ET-1)、硫代巴比妥酸反应物质(TBARS)、超氧化物歧化酶(SOD)和红细胞过氧化氢酶活性。在 W12 时,两组间无差异。在随访时,SRL 组的 PWV、cSBP、cPP 和 AIx 较低。调整血压和 eGFR 后,PWV 的差异仍有统计学意义。同时,SRL 组 ET-1 降低,而两组的 TBARS、SOD 和红细胞过氧化氢酶活性均增加,但 SRL 组增加幅度较小。我们的结果表明,基于 SRL 的 CsA 免费方案可降低肾移植受者的主动脉僵硬、血浆内皮素-1 和氧化应激,表明对动脉壁具有保护作用,可能转化为降低心血管风险。