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他克莫司治疗窗浓度与肠移植后免于急性排斥反应和移植物失功相关。

Tacrolimus time-in-therapeutic range is associated with freedom from acute rejection and graft failure following intestinal transplantation.

机构信息

Recanati-Miller Transplantation Institute, Mount Sinai Hospital, New York, NY, USA.

Department of Pharmacy, Mount Sinai Hospital, New York, NY, USA.

出版信息

Clin Transplant. 2021 Jun;35(6):e14291. doi: 10.1111/ctr.14291. Epub 2021 Apr 3.

Abstract

BACKGROUND

Trough-adjusted tacrolimus is commonly prescribed following intestinal transplantation to prevent allograft rejection. Despite established practice, there remains limited direct evidence linking tacrolimus levels with improved clinical outcomes.

METHODS

This was a single-center review of all adult non-liver containing intestinal allograft recipients from 2011 to 2018. Patients received lymphocyte depleting induction and maintenance immunosuppression consisting of tacrolimus and a corticosteroid taper. Tacrolimus time-in-therapeutic range (TAC-TTR) was calculated for all patients from the date of transplant until 1-year post-transplant using Rosendaal's method. Cox-Proportional hazards modeling was utilized to assess freedom from acute rejection and graft failure stratified by TAC-TTR quartile.

RESULTS

47 patients were included in the review. Mean TAC-TTR for the cohort was 30.2% ± 11.4. Fifteen episodes of acute rejection were observed, 8 of which were severe. Patients in the highest TAC-TTR quartile >36% had a lower incidence of acute rejection and graft failure relative to patients with a TAC-TTR <20%. Cox-Proportional hazards modeling found a 10% decrease in TAC-TTR was associated with an increased hazard for acute rejection (2.03), severe acute rejection (2.19), and graft loss (3.33).

CONCLUSION

The results of this study suggest that decreasing TAC-TTR is a risk factor for both acute rejection as well as intestinal allograft failure.

摘要

背景

肠移植术后常使用调整谷浓度的他克莫司预防移植物排斥反应。尽管已达成共识,但目前仍缺乏直接证据将他克莫司水平与改善临床结局联系起来。

方法

这是一项对 2011 年至 2018 年间所有成人非肝脏肠移植受者的单中心回顾性研究。患者接受淋巴细胞耗竭诱导和维持免疫抑制治疗,包括他克莫司和皮质类固醇的逐渐减量。使用 Rosendaal 法计算所有患者从移植日期到移植后 1 年的他克莫司治疗窗内时间(TAC-TTR)。采用 Cox 比例风险模型评估 TAC-TTR 四分位组分层的急性排斥和移植物失败的无事件率。

结果

共纳入 47 例患者。队列的平均 TAC-TTR 为 30.2%±11.4。观察到 15 例急性排斥反应,其中 8 例为重度。TAC-TTR>36%的患者急性排斥反应和移植物失败的发生率低于 TAC-TTR<20%的患者。Cox 比例风险模型发现 TAC-TTR 降低 10%与急性排斥反应(2.03)、重度急性排斥反应(2.19)和移植物丢失(3.33)的风险增加相关。

结论

本研究结果表明,降低 TAC-TTR 是急性排斥反应和肠移植失败的危险因素。

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