Masset Christophe, Lorent Marine, Kerleau Clarisse, Garandeau Claire, Houzet Aurélie, Ville Simon, Cantarovich Diego, Blancho Gilles, Giral Magali, Dantal Jacques
Service de Néphrologie et Immunologie Clinique, Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes Université, INSERM, Institute of Transplantation Urology and Nephrology, CHU Nantes, Nantes, France.
Kidney Int Rep. 2025 Feb 25;10(5):1428-1440. doi: 10.1016/j.ekir.2025.02.014. eCollection 2025 May.
Fast tacrolimus-metabolizing kidney transplant recipients (KTRs) (i.e., tacrolimus trough-level/total daily dose [C0/D < 1.05]) have poorer allograft function; however, their identification in a real-life setting is challenging. We investigated the reproducibility of tacrolimus metabolic status during the first months after transplantation and its association with long-term allograft outcomes.
All KTRs between 2000 and 2019 with a functional allograft at 1 month and receiving tacrolimus in our center were included. Fast or slow tacrolimus metabolizers were classified according to the time spent with a C0/D < 1.05 (> 75% = High, < 25% = Low) at various time points posttransplantation. We first determined the earliest accurate time for patient categorization by investigating C0/D variability during the first months. Second, a multivariate cause-specific Cox model studying allograft outcomes was performed in groups identified by their status determined from the earliest accurate timepoint after transplantation.
Among 1979 patients included in the analysis, 2 months was the earliest accurate timepoint to determine High patients (85% of High patients identified at 2 months remained High long-term, Brier score = 0.06). Multivariate analysis revealed that High patients determined at 2 months ( = 499) had a significantly higher risk of allograft loss (cause-specific hazard ratio [CS-HR] = 2.00, 95% confidence interval [CI] = 1.48-2.69) and allograft rejection (CS-HR = 1.71, 95% CI = 1.15-2.54) than Low patients after adjustment for confounding factors. Moreover, allograft function was lower in High patients (46.7 vs. 52.9 ml/min, at 3 years, < 0.0001) with a higher proportion of chronic vascular lesions at 1 year.
C0/D is a simple and pragmatic tool capable of identifying patients at risk of rejection and allograft failure as early as the second month posttransplantation.
他克莫司代谢快的肾移植受者（KTRs）（即他克莫司谷浓度/每日总剂量[C0/D]<1.05）的移植肾功能较差；然而，在现实环境中识别他们具有挑战性。我们研究了移植后最初几个月他克莫司代谢状态的可重复性及其与长期移植结局的关联。
纳入2000年至2019年间在我们中心移植1个月时移植肾功能正常且接受他克莫司治疗的所有KTRs。根据移植后不同时间点C0/D<1.05的时间占比（>75% = 高，<25% = 低）将他克莫司代谢快或慢的患者进行分类。我们首先通过研究最初几个月C0/D的变异性来确定患者分类的最早准确时间。其次，对根据移植后最早准确时间点确定的状态分组的患者进行了研究移植结局的多变量特定病因Cox模型分析。
在纳入分析的1979例患者中，2个月是确定代谢快患者的最早准确时间点（2个月时确定的代谢快患者中85%长期保持代谢快，Brier评分 = 0.06）。多变量分析显示，在调整混杂因素后，2个月时确定的代谢快患者（n = 499）发生移植肾丢失（特定病因风险比[CS-HR]=2.00，95%置信区间[CI]=1.48 - 2.69）和移植肾排斥反应（CS-HR =
