Higher Variability of Tacrolimus Trough Level Increases Risk of Acute Rejection in Kidney Transplant Recipients.

Background: Tacrolimus is the most commonly prescribed immunosuppressive drug after kidney transplantation (KTx). The trough level of tacrolimus (T0) is currently used for routine monitoring after KTx. The purpose of this study was to examine the association between the variability of T0 and acute rejection.

Methods: All kidney transplant recipients (KTR) with tacrolimus-based regimen and episode of biopsy-proven acute rejection (BPAR) between January 2012 and October 2014 were enrolled in the acute rejection (AR) group. KTR with tacrolimus-based regimen and without episode of AR were enrolled in the control group. All of the results of T0 within 6 months before episode of acute rejection were used for the calculation of within-patient variability of T0. The percent coefficient of variation, which is calculated as (standard deviation of mean/mean) × 100%, was used to represent the concentration variability of tacrolimus.

Results: In all, 25 KTR with AR and another 136 KTR without BPAR were enrolled in the study. The mean age of all 161 patients was 50.1 ± 10.4 years, and the mean duration after KTx was 4.3 ± 4.7 years. The average daily dose of tacrolimus was 5.7 ± 2.6 mg, and T0 was 5.4 ± 1.8 ng/mL. Age, sex, duration after KTx, daily dose of tacrolimus, and T0 were similar in both groups. Compared with the control group, the percent coefficient of variation of T0 was significantly higher in patients with BPAR 12.1% ± 7.9% vs 39% ± 15.6%, P<.001.

Conclusions: The study results suggest that, in KTR, higher variability of tacrolimus trough level is associated with higher risk of acute rejection.