Impact of Tacrolimus Trough Levels at Discharge on Early Post-Kidney Transplantation Outcomes: A Nationwide Cohort Study

<b>Introduction</b>: Tacrolimus is a cornerstone immunosuppressant in kidney transplantation (KT), but its narrow therapeutic index necessitates precise monitoring. Early post-transplant tacrolimus trough concentrations (C0) are critical, as suboptimal levels can increase rejection and infection risks. This study evaluated the impact of C0 levels at discharge on early post-transplant outcomes in a large Korean cohort. <b>Materials and Methods</b>: This retrospective analysis included 5293 KT recipients from the Korean Organ Transplant Registry (KOTRY) who received a kidney transplant between 2014 and 2019. Recipients were categorized into three groups based on C0 levels at discharge: <5.9 ng/mL, 5.9-9.5 ng/mL, and >9.5 ng/mL. Clinical outcomes, including serum creatinine (sCr), biopsy-proven acute rejection (BPAR), and infections requiring hospitalization, were analyzed using the Kruskal-Wallis test and chi-squared test. <b>Results</b>: The BPAR rates were 22.5%, 20.9%, and 21.5% for the low, middle, and high C0 groups, respectively (<i>p</i> = 0.221). However, the incidence of infections requiring hospitalization was significantly higher in the high C0 group (28.1%) compared to the middle (23.9%) and low (21.7%) groups at 1-year follow-up (<i>p</i> < 0.001). In high-risk recipients, lower C0 levels correlated with increased BPAR rates (33.9% vs. 29.1% and 26.4%, <i>p</i> = 0.030). Higher intrapatient variability (IPV) between discharge and 6 months was linked to higher infection risk in all recipients and increased BPAR and infection risk in high-risk patients. <b>Conclusions</b>: Optimal C0 levels at discharge are essential to balance rejection and infection risks in KT. Lower C0 levels and higher IPV increase the risk of adverse outcomes, especially in high-risk sensitized recipients, underscoring the need for careful monitoring and personalized management.