Tacrolimus Predose Concentrations Do Not Predict the Risk of Acute Rejection After Renal Transplantation: A Pooled Analysis From Three Randomized-Controlled Clinical Trials
Tacrolimus Predose Concentrations Do Not Predict the Risk of Acute Rejection After Renal Transplantation: A Pooled Analysis From Three Randomized-Controlled Clinical Trials
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DOI：
10.1111/ajt.12191
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发表时间：
2013-05-01
影响因子：
8.8
通讯作者：
van Gelder, T.
中科院分区：
文献类型：
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作者：
Bouamar, R.;Shuker, N.;van Gelder, T.
他克莫司（Tac）的治疗药物监测（TDM）已得到普遍应用。然而，Tac的浓度-效应关系定义不明确。本研究调查了Tac浓度是否与肾移植受者的急性排斥反应有关。汇总了三项大型试验的数据。我们使用单变量和多变量分析来研究活检证实的急性排斥反应（BPAR）和5个时间点（移植后第3、10和14天，以及第1和6个月）的Tac给药前浓度之间的关系。共有136/1304例患者发生BPAR，总发生率为10.4%。我们没有发现Tac给药前浓度与不同时间点BPAR发生率之间存在任何显著相关性。在多变量分析中，只有移植肾功能延迟恢复（DGF）和诱导治疗的使用与BPAR独立相关，DGF的比值比为2.7 [95% CI：1.84.0; p < 0.001]，诱导治疗的比值比为0.66 [95% CI：0.440.99; p = 0.049]。其他变量，包括Tac给药前浓度，与BPAR无统计学显著相关性。我们没有发现在肾移植后5个时间点测量的Tac给药前浓度与此后发生的急性排斥反应的发生率之间存在关联。根据本研究，无法确定Tac的最佳靶浓度。
Therapeutic drug monitoring (TDM) for tacrolimus (Tac) is universally applied. However, the concentrationeffect relationship for Tac is poorly defined. This study investigated whether Tac concentrations are associated with acute rejection in kidney transplant recipients. Data from three large trials were pooled. We used univariate and multivariate analysis to investigate the relationship between biopsy-proven acute rejection (BPAR) and Tac predose concentration at five time points (day 3, 10 and 14, and month 1 and 6 after transplantation). A total of 136/1304 patients experienced BPAR, giving an overall incidence of 10.4%. We did not find any significant correlations between Tac predose concentrations and the incidence of BPAR at the different time points. In the multivariate analysis, only delayed graft function (DGF) and the use of induction therapy were independently correlated with BPAR, with an odds ratio of 2.7 [95% CI: 1.84.0; p < 0.001] for DGF and 0.66 [95% CI: 0.440.99; p = 0.049] for induction therapy. The other variables, including the Tac predose concentrations, were not statistically significantly associated with BPAR. We did not find an association between the Tac predose concentrations measured at five time points after kidney transplantation and the incidence of acute rejection occurring thereafter. Based on this study it is not possible to define the optimal target concentrations for Tac.