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

Arlisson Macedo Rodrigues, Mariana Tavares Tanno, Mariana Moraes Contti, Hong Si Nga, Mariana Farina Valiatti, Silvana Daher Costa, Tainá Veras de Sandes-Freitas, Ronaldo de Matos Esmeraldo, Camila Marinho Assunção, Juliana Bastos Campos Tassi, Gustavo Fernandes Ferreira, Claudia Rosso Felipe, Jose Osmar Medina Pestana, Helio Tedesco Silva, Luis Gustavo Modelli de Andrade
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Abstract

Introduction The 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. Methods Multicenter 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. Results The 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. Discussion The 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.
不同KDPI范围的供者肾移植12个月肾功能比较他克莫司和麦考酚酸与他克莫司和mTORi。一项使用倾向评分的多中心队列研究
在TRANSFORM试验中,与他克莫司/霉酚酸酯(MMF)相比,他克莫司/mTORi联合用药是安全的。然而,对于高KDPI(肾脏供者概况指数)的供者,没有数据支持该方案的有效性。本研究的主要目的是探讨KDPI对mTORi或MMF患者12个月肾功能(eGFR)的影响。方法对巴西4家使用他克莫司联合mTORi治疗方案的医院进行多中心队列研究。收集了2008年至2018年18岁以上肾移植受者他克莫司/霉酚酸酯(MMF)和他克莫司/mTORi (mTORi)方案的数据。为了更好的同质性,使用倾向评分。之后,用于分组选择(“匹配”)的方法是k最近邻(KNN)方法。对这个新的平衡样本进行了新的分析,并根据中位数KDPI构成了两个不同的子样本。结果全球分析(n = 870)显示肾功能恶化的主要决定因素是高KDPI。随后,对三层进行了分析。在第一阶段(KDPI为50),242例患者接受评估,每组121例。mTORi组的eGFR为64 ml/min/1.73 m2,而MMF组为63 ml/min/1.73 m2, p = 0.4,当计算eGFR时,mTORi组为61 ml/min, MMF组为53 ml/min, p = 0.065。在第二阶段(KDPI从50到85),282例患者被评估,每组141例。mTORi组eGFR为46 ml/min/1.73 m2,而MMF组为48 ml/min/1.73 m2, p = 0.4,当计算eGFR时,mTORi组为40 ml/min, MMF组为41 ml/min, p = 0.8。在最后一层(KDPI高于85),n = 126,每组63例,mTORi的eGFR为36 ml/min/1.73 m2,而MMF为39 ml/min/1.73 m2, p = 0.2,当估算估算eGFR时,mTORi为30 ml/min, MMF为34,p = 0.2。与标准方案相比,使用mTOR抑制剂的方案是一种有效且安全的方案。此外,该方案似乎提供了额外的预防感染的保护,并可能是这些疾病高风险病例的重要盟友。
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