Egeland Erlend Johannessen, Robertsen Ida, Hermann Monica, Midtvedt Karsten, Størset Elisabet, Gustavsen Marte Theie, Reisæter Anna Varberg, Klaasen Rolf, Bergan Stein, Holdaas Hallvard, Hartmann Anders, Åsberg Anders
1 School of Pharmacy, University of Oslo, Oslo, Norway. 2 Western Norway University of Applied Sciences, Norway. 3 Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. 4 Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 5 Department of Pharmacology, Oslo University Hospital, Oslo, Norway.
Transplantation. 2017 Aug;101(8):e273-e279. doi: 10.1097/TP.0000000000001796.
Patients with high tacrolimus clearance eliminate more drug within a dose interval compared with those with low clearance. Delays in dosing time will result in transient periods of lower concentrations in high versus low clearance patients. Transient subtherapeutic tacrolimus concentrations may induce acute rejection episodes.
A retrospective study in all renal transplant patients treated with tacrolimus at our center from 2009 to 2013 was conducted. The association between individually estimated tacrolimus clearance (daily tacrolimus dose [mg]/trough concentration [μg/L]) and biopsy-proven acute rejection (BPAR) the first 90 days posttransplantation was investigated.
In total, 638 patients treated with oral tacrolimus were included in the analysis. Eighty-five (13.3%) patients experienced BPAR. Patients were stratified into 4 groups per their estimated clearance. The patients in the high clearance group had significantly higher incidence of BPAR (20.6%) with a hazard ratio of 2.39 (95% confidence interval, 1.30-4.40) compared with the low clearance group. Clearance estimate (as a continuous variable) showed a hazard ratio of 2.25 (95% confidence interval, 1.70-2.99) after adjusting for other risk factors. There were no significant differences in neither trough concentrations the first week after transplantation nor time to target trough concentration between patients later experiencing BPAR or not.
High estimated clearance is significantly associated with increased risk of BPAR the first 90 days posttransplantation and may predict an increased risk of rejection in the early phase after renal transplantation.
与低清除率患者相比，他克莫司清除率高的患者在一个给药间隔内清除的药物更多。给药时间延迟会导致高清除率患者与低清除率患者相比出现血药浓度较低的短暂时期。他克莫司血药浓度短暂低于治疗水平可能会引发急性排斥反应。
对2009年至2013年在本中心接受他克莫司治疗的所有肾移植患者进行了一项回顾性研究。研究了个体估算的他克莫司清除率（每日他克莫司剂量[mg]/谷浓度[μg/L]）与移植后前90天经活检证实的急性排斥反应（BPAR）之间的关联。
总计638例接受口服他克莫司治疗的患者纳入分析。85例（13.3%）患者发生BPAR。根据估算的清除率将患者分为4组。与低清除率组相比，高清除率组患者的BPAR发生率显著更高（20.6%），风险比为2.39（95%置信区间，1.30 - 4.40）。在调整其他风险因素后，清除率估算值（作为连续变量）的风险比为2.25（95%置信区间，1.70 - 2.99）。移植后第一周的谷浓度以及达到目标谷浓度的时间在后来发生BPAR的患者与未发生BPAR的患者之间均无显著差异。
估算的高清除率与移植后前90天BPAR风险增加显著相关，并且可能预示肾移植后早期排斥反应风险增加。
