Hospital Universitario Virgen del Rocío, Spain.
Medicina Digestiva, Hospital Universitari i Politècnic La Fe, España.
Rev Esp Enferm Dig. 2022 Jun;114(6):335-342. doi: 10.17235/reed.2022.8549/2021.
reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and impact of everolimus plus reduced tacrolimus (EVR + rTAC) vs. mycophenolate mofetil plus tacrolimus (MMF + TAC) on kidney function in LT recipients from Spain.
the REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post-transplantation to receive EVR + rTAC (TAC levels ≤ 5 ng/mL) or to continue with MMF + TAC (TAC levels = 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated.
in the EVR + rTAC group (n = 105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73 m2 to 86.1 [27.9] mL/min/1.73 m2) whereas it decreased in the MMF + TAC (n = 106) group (88.4 [34.3] mL/min/1.73 m2 to 83.2 [25.2] mL/min/1.73 m2), with significant (p < 0.05) differences in eGFR throughout the study. However, both groups had a similar clinical benefit regarding renal function (improvement in 18.6 % vs. 19.1 %, and stabilization in 81.4 % vs. 80.9 % of patients in the EVR + rTAC vs. MMF + TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7 % vs. 3.8 %), deaths (5.7 % vs. 2.8 %), and serious adverse events (51.9 % vs. 44.0 %) between the 2 groups.
EVR + rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation.
降低钙调磷酸酶抑制剂水平被认为是降低肝移植（LT）受者肾功能障碍发生率的关键。本研究旨在评估依维莫司联合低剂量他克莫司（EVR + rTAC）与霉酚酸酯联合他克莫司（MMF + TAC）对来自西班牙的 LT 受者肾功能的安全性和影响。
REDUCE 研究是一项 52 周、多中心、随机、对照、开放标签、3b 期研究，纳入肝移植术后 28 天的初治 LT 受者。符合条件的患者在移植后 28 天随机（1:1）分为两组，分别接受 EVR + rTAC（TAC 水平≤5ng/ml）或继续使用 MMF + TAC（TAC 水平=6-10ng/ml）。评估平均估算肾小球滤过率（eGFR）、肾功能临床获益和安全性。
在 EVR + rTAC 组（n=105）中，eGFR 从随机分组到第 52 周时增加（82.2[28.5]ml/min/1.73m2 至 86.1[27.9]ml/min/1.73m2），而 MMF + TAC 组（n=106）则降低（88.4[34.3]ml/min/1.73m2 至 83.2[25.2]ml/min/1.73m2），整个研究期间 eGFR 差异具有统计学意义（p<0.05）。然而，两组在肾功能方面均具有相似的临床获益（EVR + rTAC 组分别有 18.6%和 81.4%的患者改善和稳定，MMF + TAC 组分别有 19.1%和 80.9%）。两组急性排斥反应（5.7%vs.3.8%）、死亡（5.7%vs.2.8%）和严重不良事件（51.9%vs.44.0%）发生率无显著差异。
EVR + rTAC 可安全降低肝移植受者他克莫司的暴露量，显著改善 eGFR，但肝移植 1 年后肾功能的临床获益无显著差异。
