Division of Nephrology, Department of Internal Medicine, Konyang University Hospital, College of Medicine, Konyang University, Daejeon, South Korea.
Transplantation Research Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Front Immunol. 2021 Sep 30;12:746013. doi: 10.3389/fimmu.2021.746013. eCollection 2021.
This study aimed to determine the impact of tacrolimus (TAC) trough level (C0) intrapatient variability (IPV) over a period of 2 years after kidney transplantation (KT) on allograft outcomes. In total, 1,143 patients with low immunologic risk were enrolled. The time-weighted coefficient variability (TWCV) of TAC-C0 was calculated, and patients were divided into tertile groups (T1: < 24.6%, T2: 24.6%-33.7%, T3: ≥ 33.7%) according to TAC-C0-TWCV up to post-transplant 1 year. They were classified into the low/low, low/high, high/low, and high/high groups based on a TAC-C0-TWCV value of 33.7% during post-transplant 0-1 and 1-2 years. The allograft outcomes among the three tertile and four TAC-C0-TWCV groups were compared. The T3 group had the highest rate of death-censored allograft loss (DCGL), and T3 was considered an independent risk factor for DCGL. The low/low group had the lowest and the high/high group had the highest risk for DCGL. Moreover, patients with a mean TAC-C0 of ≥5 ng/ml in the high/high group were at the highest risk for DCGL. Thus, TAC-IPV can significantly affect allograft outcomes even with a high mean TAC-C0. Furthermore, to improve allograft outcomes, a low TAC-IPV should be maintained even after the first year of KT.
本研究旨在确定肾移植（KT）后 2 年内他克莫司（TAC）谷浓度（C0）个体内变异（IPV）对移植物结局的影响。共纳入 1143 例低免疫风险患者。计算 TAC-C0 的时间加权变异系数（TWCV），并根据 TAC-C0-TWCV 将患者分为三分位组（T1：<24.6%，T2：24.6%-33.7%，T3：≥33.7%），直至移植后 1 年。根据移植后 0-1 年和 1-2 年 TAC-C0-TWCV 值为 33.7%，将患者分为低/低、低/高、高/低和高/高组。比较三组和四组 TAC-C0-TWCV 组的移植物结局。T3 组的死亡风险调整移植物丢失（DCGL）发生率最高，T3 被认为是 DCGL 的独立危险因素。低/低组的 DCGL 风险最低，高/高组的 DCGL 风险最高。此外，高/高组中 TAC-C0 均值≥5ng/ml 的患者 DCGL 风险最高。因此，即使 TAC-C0 均值较高，TAC-IPV 也可显著影响移植物结局。此外，为改善移植物结局，即使在 KT 后 1 年内，也应保持低 TAC-IPV。
