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肾移植后第一周内的他克莫司浓度与急性排斥反应有关。

Trough tacrolimus concentrations in the first week after kidney transplantation are related to acute rejection.

机构信息

Clinical Pharmacology Service, School of Medicine, Autonomous University of Madrid, Madrid, Spain.

出版信息

Ther Drug Monit. 2009 Aug;31(4):436-42. doi: 10.1097/FTD.0b013e3181a8f02a.

Abstract

There is evidence showing the importance of reaching immunosuppressant target concentrations as soon as possible. The aim of this study was to evaluate the relationship between tacrolimus trough concentrations within the first week after transplantation and the rate of acute rejection. In this descriptive-analytic study, we included 57 renal transplant patients receiving tacrolimus as the primary immunosuppressive drug. After univariate analysis, donor age, duration of hospital stay, and creatinine clearance (third month) showed significant differences between rejecters and nonrejecters. In addition, mean tacrolimus trough concentrations on day 5, day 7, mean of days 1-7, and mean of days 5-7 were found to be significantly lower in rejecters (P = 0.009, P = 0.012, P = 0.006, and P = 0.035, respectively). Receiver operating characteristic curve analysis with tacrolimus trough concentrations measured on days 5 and 7 was able to discriminate between patients with and without acute rejection (P = 0.028 and P = 0.048 after Bonferroni correction). The tacrolimus trough concentration with the best sensitivity-specificity balance was 9.3 ng/mL on day 5 and 8.7 ng/mL on day 7. In the Kaplan-Meier analysis, patients with tacrolimus trough concentrations below 9.3 mg/mL on day 5 showed a lower survival time without acute rejection (P = 0.048 after correction) in comparison with patients with tacrolimus trough concentrations above this concentration. After logistic regression, we obtained a model relating rejection with sex, donor age, and tacrolimus trough concentrations on day 5 (P = 0.004). No significant relationship between tacrolimus trough concentrations and delta creatinine clearance from week 1 to month 3 was obtained. These results confirm that tacrolimus trough concentrations during the first week are an important predictor of acute rejection. Therefore, it is critical to reach target blood concentrations of tacrolimus as soon as possible to improve allograft survival.

摘要

有证据表明尽快达到免疫抑制剂的目标浓度非常重要。本研究旨在评估移植后第一周内他克莫司谷浓度与急性排斥反应率之间的关系。在这项描述性分析研究中,我们纳入了 57 名接受他克莫司作为主要免疫抑制剂的肾移植患者。在单因素分析后,发现排斥者和非排斥者之间在供体年龄、住院时间和肌酐清除率(第 3 个月)方面存在显著差异。此外,发现排斥者在第 5 天、第 7 天、第 1-7 天的平均日浓度和第 5-7 天的平均日浓度均显著较低(P=0.009、P=0.012、P=0.006 和 P=0.035)。在接受 Bonferroni 校正后,使用第 5 天和第 7 天的他克莫司谷浓度进行的受试者工作特征曲线分析能够区分有和无急性排斥反应的患者(P=0.028 和 P=0.048)。第 5 天和第 7 天的他克莫司谷浓度具有最佳的敏感性特异性平衡,分别为 9.3ng/mL 和 8.7ng/mL。在 Kaplan-Meier 分析中,与他克莫司谷浓度高于该浓度的患者相比,第 5 天他克莫司谷浓度低于 9.3mg/mL 的患者无急性排斥反应的生存时间更短(校正后 P=0.048)。在逻辑回归后,我们获得了一个与性别、供体年龄和第 5 天他克莫司谷浓度有关的排斥反应模型(P=0.004)。未发现第 1 周到第 3 个月的他克莫司谷浓度与肌酐清除率的差值之间存在显著关系。这些结果证实,第 1 周内的他克莫司谷浓度是急性排斥反应的一个重要预测指标。因此,尽快达到他克莫司的目标血药浓度对于提高移植物存活率至关重要。

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