AKH Wien, Vienna, Austria.
Am J Transplant. 2012 Sep;12(9):2487-97. doi: 10.1111/j.1600-6143.2012.04131.x. Epub 2012 Jul 9.
This randomized, comparative, multinational phase 3b/4 study of patients 1-8 years postcardiac transplantation (mean 3.9 years) evaluated the effect of conversion from a calcineurin inhibitor (CNI) to sirolimus on renal function in patients with renal insufficiency. In total, 116 patients on CNI therapy with GFR 40-90 mL/min/1.73 m(2) were randomized (1:1) to sirolimus (n = 57) or CNI (n = 59). Intent-to-treat analysis showed the 1-year adjusted mean change from baseline in creatinine clearance (Cockcroft-Gault) was significantly higher with sirolimus versus CNI treatment (+3.0 vs. -1.4 mL/min/1.73 m(2) , respectively; p = 0.004). By on-therapy analysis, values were +4.7 and -2.1, respectively (p < 0.001). Acute rejection (AR) rates were numerically higher in the sirolimus group; 1 AR with hemodynamic compromise occurred in each group. A significantly higher treatment discontinuation rate due to adverse events (AEs; 33.3% vs. 0%; p < 0.001) occurred in the sirolimus group. Most common treatment-emergent AEs significantly higher in the sirolimus group were diarrhea (28.1%), rash (28.1%) and infection (47.4%). Conversion to sirolimus from CNI therapy improved renal function in cardiac transplant recipients with renal impairment, but was associated with an attendant AR risk and higher discontinuation rate attributable to AEs.
这项随机、对照、多国 3b/4 期研究纳入了心脏移植后 1-8 年（平均 3.9 年）的患者，评估了将钙调磷酸酶抑制剂（CNI）转换为西罗莫司对肾功能不全患者的肾功能的影响。共有 116 名 CNI 治疗且肾小球滤过率（GFR）为 40-90ml/min/1.73m²的患者被随机（1:1）分为西罗莫司组（n=57）或 CNI 组（n=59）。意向治疗分析显示，与 CNI 治疗相比，西罗莫司治疗 1 年时的肌酐清除率（Cockcroft-Gault）的平均调整后基线变化明显更高（分别为+3.0 vs. -1.4ml/min/1.73m²，p=0.004）。根据治疗分析，数值分别为+4.7 和-2.1（p<0.001）。西罗莫司组的急性排斥反应（AR）发生率较高，每组各有 1 例因血流动力学障碍而发生 AR。西罗莫司组因不良事件（AE）导致的治疗停药率明显更高（33.3% vs. 0%，p<0.001）。西罗莫司组最常见的治疗后出现的 AE 显著更高，包括腹泻（28.1%）、皮疹（28.1%）和感染（47.4%）。从 CNI 治疗转换为西罗莫司可改善肾功能不全的心脏移植受者的肾功能，但与 AR 风险增加和因 AE 导致的停药率升高有关。
