Table1_Renal function at 12 months of kidney transplantation comparing tacrolimus and mycophenolate with tacrolimus and mTORi in donors with different KDPI ranges. A multicenter cohort study using propensity scoring.docx

IntroductionThe combination of tacrolimus/mTORi compared to tacrolimus/mycophenolate (MMF) was shown to be safe in the TRANSFORM trial. For donors with a high KDPI (Kidney Donor Profile Index), however, there are no data to support the effectiveness of this regimen. The main objective of this study was to explore the influence of the KDPI on 12-month renal function (eGFR) in patients receiving mTORi or MMF.
MethodsMulticenter cohort study of four Brazilian services that use the tacrolimus with mTORi as a protocol. Data from 2008 to 2018 of the tacrolimus/mycophenolate (MMF) and tacrolimus/mTORi (mTORi) regimens in renal transplant recipients over 18 years old were collected. For better homogeneity, the propensity score was used. Afterward, the method used for group selection (“match”) was the K-nearest neighbor (KNN) method. New analyses were performed on this new balanced sample, and two different subsamples were constituted based on the median KDPI.
ResultsThe global analysis (n = 870) showed that the major determinant of worse kidney function was high KDPI. Afterward, the three strata were analyzed. In the first stratum (KDPI up to 50), 242 patients were evaluated, with 121 in each group. The eGFR was 64 ml/min/1.73 m2 in the mTORi group compared to 63 in the MMF group, p = 0.4, and when imputed eGFR was evaluated, 61 in the mTORi and 53 in the MMF, p = 0.065. In the second stratum (KDPI from 50 to 85), 282 patients were evaluated, with 141 in each group. eGFR was 46 ml/min/1.73 m2 in mTORi compared to 48 in MMF, p = 0.4, and when imputed eGFR was evaluated, 40 mTORi and 41 MMF, p = 0.8. In the last stratum (KDPI higher than 85) with n = 126 and 63 cases per group, eGFR was 36 ml/min/1.73 m2 in mTORi compared to 39 in MMF, p = 0.2, and when imputed eGFR was evaluated, 30 mTORi and 34 MMF, p = 0.2.
DiscussionThe regimen using mTOR inhibitor is an effective and safe regimen when compared to the standard regimen. In addition, the scheme seems to offer additional protection against infections and may be an important ally in cases of high risk for these pathologies.

引言：在TRANSFORM试验中，他克莫司联合哺乳动物雷帕霉素靶蛋白抑制剂（mTOR inhibitor, mTORi）的免疫抑制方案相较于他克莫司联合麦考酚酯（mycophenolate, MMF）方案已被证实安全。然而，对于肾供体概况指数（Kidney Donor Profile Index, KDPI）较高的供体，尚无数据支持该联合方案的临床有效性。本研究的主要目的是探究KDPI对接受mTORi或MMF治疗的18岁以上肾移植受者12个月肾功能（估算肾小球滤过率, eGFR）的影响。
方法：本研究为多中心队列研究，纳入巴西4家采用他克莫司联合mTORi作为标准免疫抑制方案的医疗中心。研究收集了2008年至2018年间，18岁以上肾移植受者接受他克莫司/麦考酚酯（MMF）与他克莫司/mTORi两种方案的临床数据。为提升研究队列的同质性，本研究采用倾向得分法进行校正，随后通过K近邻（K-nearest neighbor, KNN）法完成组间匹配。基于此新的平衡样本开展后续分析，并依据KDPI中位数将样本划分为两个亚组。
结果：总体分析（n=870）显示，肾功能恶化的主要影响因素为KDPI升高。随后对三个分层队列进行分析：第一分层队列（KDPI≤50）共纳入242例患者，两组各121例。mTORi组的eGFR为64 ml/min/1.73m²，MMF组为63 ml/min/1.73m²（p=0.4）；经插补的eGFR评估显示，mTORi组为61，MMF组为53（p=0.065）。第二分层队列（50<KDPI≤85）共纳入282例患者，两组各141例。mTORi组eGFR为46 ml/min/1.73m²，MMF组为48 ml/min/1.73m²（p=0.4）；经插补的eGFR评估显示，mTORi组为40，MMF组为41（p=0.8）。第三分层队列（KDPI>85）共纳入126例患者，两组各63例。mTORi组eGFR为36 ml/min/1.73m²，MMF组为39 ml/min/1.73m²（p=0.2）；经插补的eGFR评估显示，mTORi组为30，MMF组为34（p=0.2）。
讨论：与标准免疫抑制方案相比，采用mTOR抑制剂的联合方案安全有效。此外，该方案似乎可额外提供感染防护，在感染风险较高的病例中可作为重要的治疗选择。