Taber David J, Su Zemin, Fleming James N, McGillicuddy John W, Posadas-Salas Maria A, Treiber Frank A, Dubay Derek, Srinivas Titte R, Mauldin Patrick D, Moran William P, Baliga Prabhakar K
Division of Transplant Surgery, Medical University of South Carolina, Charleston, SC.
Department of Pharmacy Services, Ralph H Johnson VAMC, Charleston, SC.
Transplantation. 2017 Dec;101(12):2931-2938. doi: 10.1097/TP.0000000000001840.
Low tacrolimus concentrations have been associated with higher risk of acute rejection, particularly within African American (AA) kidney transplant recipients; little is known about intrapatient tacrolimus variabilities impact on racial disparities.
Ten year, single-center, longitudinal cohort study of kidney recipients. Intrapatient tacrolimus variability was assessed using the coefficient of variation (CV) measured between 1 month posttransplant and the clinical event, with a comparable period assessed in those without events. Pediatrics, nontacrolimus/mycophenolate regimens, and nonrenal transplants were excluded. Multivariable Cox regression models were used to analyze data.
One thousand four hundred eleven recipients were included (54.4% AA) with 39 521 concentrations used to assess intrapatient tacrolimus CV. Overall, intrapatient tacrolimus CV was higher in AAs versus non-AAs (39.9 ± 19.8 % vs 34.8 ± 15.8% P < 0.001). Tacrolimus variability was a significant risk factor for deleterious clinical outcomes. A 10% increase in tacrolimus CV augmented the risk of acute rejection by 20% (adjusted hazard ratio, 1.20, 1.13-1.28; P < 0.001) and the risk of graft loss by 30% (adjusted hazard ratio, 1.30, 1.23-1.37; P < 0.001), with significant effect modification by race for acute rejection, but not graft loss. High tacrolimus variability (CV >40%) was a significant explanatory variable for disparities in AAs; the crude relative risk of acute rejection in AAs was reduced by 46% when including tacrolimus variability in modeling and reduced by 40% for graft loss.
These data demonstrate that intrapatient tacrolimus variability is strongly associated with acute rejection in AAs and graft loss in all patients. Tacrolimus variability is a significant explanatory variable for disparities in AA recipients.
他克莫司浓度较低与急性排斥反应风险较高相关，尤其是在非裔美国（AA）肾移植受者中；关于患者体内他克莫司变异性对种族差异的影响知之甚少。
对肾移植受者进行为期十年的单中心纵向队列研究。使用移植后1个月至临床事件期间测得的变异系数（CV）评估患者体内他克莫司的变异性，并在无事件发生的患者中评估可比时间段。排除儿科患者、非他克莫司/霉酚酸酯治疗方案和非肾移植患者。使用多变量Cox回归模型分析数据。
纳入1411名受者（54.4%为AA），使用39521个浓度评估患者体内他克莫司CV。总体而言，AA患者的他克莫司CV高于非AA患者（39.9±19.8%对34.8±15.8%，P<0.001）。他克莫司变异性是有害临床结局的重要危险因素。他克莫司CV增加10%会使急性排斥反应风险增加20%（调整后风险比，1.20，1.13 - 1.28；P<0.001），使移植肾丢失风险增加30%（调整后风险比，1.30，1.23 - 1.37；P<0.001），种族对急性排斥反应有显著的效应修正作用，但对移植肾丢失没有。高他克莫司变异性（CV>40%）是AA患者差异的重要解释变量；在建模中纳入他克莫司变异性时，AA患者急性排斥反应的粗相对风险降低了46%，移植肾丢失风险降低了40%。
这些数据表明，患者体内他克莫司变异性与AA患者的急性排斥反应以及所有患者的移植肾丢失密切相关。他克莫司变异性是AA受者差异的重要解释变量。
