High tacrolimus intrapatient variability has been associated with inferior graft outcomes in patients with kidney transplants. We studied baseline patterns of tacrolimus intrapatient variability in pediatric patients with kidney transplants and examined these patterns in relation to C1q-binding de novo donor-specific antibodies.

All tacrolimus levels in participants who underwent kidney-only transplantation at a single pediatric center from 2004 to 2018 (with at least 12-month follow-up, followed until 2019) were analyzed to determine baseline variability. Intrapatient variability was defined using the coefficient of variation (SD/mean x100%) of all samples in a 6-month moving window. Routine de novo donor-specific antibody measurements were available for a subgroup of patients transplanted in 2010–2018. Cox proportional hazards models using tacrolimus intrapatient variability as a time-varying variable were used to examine the association between intrapatient variability and graft outcomes. The primary outcome of interest was C1q-binding de novo donor-specific antibody formation.

Tacrolimus intrapatient variability developed a steady-state baseline of 30% at 10 months post-transplant in 426 patients with a combined 31,125 tacrolimus levels. Included in the outcomes study were 220 patients, of whom 51 developed C1q-binding de novo donor-specific antibodies. De novo donor-specific antibody formers had higher intrapatient variability, with a median of 38% (interquartile range, 28%–48%) compared with 28% (interquartile range, 20%–38%) for nondonor-specific antibody formers (P<0.001). Patients with high tacrolimus intrapatient variability (coefficient of variation >30%) had higher risk of de novo donor-specific antibody formation (hazard ratio, 5.35; 95% confidence interval, 2.45 to 11.68). Patients in the top quartile of tacrolimus intrapatient variability (coefficient of variation >41%) had the strongest association with C1q-binding de novo donor-specific antibody formation (hazard ratio, 11.81; 95% confidence interval, 4.76 to 29.27).

High tacrolimus intrapatient variability was strongly associated with de novo donor-specific antibody formation.

他克莫司患者体内的高变异性与肾移植患者的移植结果较差有关。我们研究了肾移植儿科患者他克莫司患者体内变异的基线模式，并检查了这些模式与 C1q 结合从头供体特异性抗体的关系。

对 2004 年至 2018 年在单个儿科中心接受纯肾移植的参与者（至少随访 12 个月，随访至 2019 年）的所有他克莫司水平进行了分析，以确定基线变异性。使用6 个月移动窗口中所有样本的变异系数（SD/平均值x 100%）定义患者内部变异性。对 2010 年至 2018 年移植的一个亚组患者进行了常规的从头供体特异性抗体测量。使用他克莫司患者体内变异性作为时变变量的 Cox 比例风险模型用于检查患者体内变异性与移植结果之间的关联。感兴趣的主要结果是 C1q 结合从头供体特异性抗体的形成。

移植后 10 个月，426 名患者的他克莫司患者体内变异性达到了 30% 的稳态基线，总共 31,125 个他克莫司水平。结果研究包括 220 名患者，其中 51 名患者从头产生了 C1q 结合供体特异性抗体。从头供体特异性抗体形成物具有较高的患者内变异性，中位数为 38%（四分位距，28%–48%），而非供体特异性抗体形成物的中位数为 28%（四分位距，20%–38%）（P <0.001）。他克莫司患者体内变异性较高（变异系数>30%）的患者从头形成供者特异性抗体的风险较高（风险比，5.35；95%置信区间，2.45至11.68）。他克莫司患者体内变异性排名前四分之一的患者（变异系数 >41%）与 C1q 结合从头供体特异性抗体形成的相关性最强（风险比，11.81；95% 置信区间，4.76 至 29.27）。

他克莫司患者体内的高变异性与从头供体特异性抗体的形成密切相关。