Impact of Early vs. Delayed Tacrolimus Initiation on Clinical Outcomes in Deceased-Donor Kidney Transplantation with Thymoglobulin Induction

Background: Thymoglobulin has been beneficial in the allograft recovery by delaying the exposure to tacrolimus in patients with delayed recovery of graft function (DGF) after deceased donor kidney transplantation (DDKT). Delaying tacrolimus may negatively affect transplant outcomes, but the effect is uncertain. Methods: We performed 126 DDKT recipients with thymoglobulin among 395 KTRs from September, 2013 to September, 2020. This study aims to evaluate the impact of early versus delayed tacrolimus initiation on clinical outcomes in DDKT with thymoglobulin induction. We divided them into two groups: early tacrolimus initiation (n=33) and delayed tacrolimus initiation (n=93) based on the tacrolimus timing. We investigated allograft function at the early and late period of time after KT, the rate of DGF, acute rejection within 1 year after KT, infection, death-censored graft survival, and patient survival. Results: The baseline characteristics were not different between them. There were no significant differences of human leukocyte antigen mismatch numbers, the proportion of patients with panel reactive antibody > 50%, or the presence of preformed donor-specific antibody (DSA). The delayed initiation group had a higher incidence of DGF compared to the early initiation group. Allograft function was worse in the early initiation group than in the delayed group at the early post-transplant period, but this difference disappeared in the later post-transplant period. Delayed initiation group showed a higher frequency of acute rejection within 1 year after KT, the development of de novo DSA, and lower death-censored graft survival rate compared to the delayed initiation group. There were no significant differences in the development of infection like cytomegalovirus or BK virus, and patient survival rate between them. Conclusion: Delayed initiation of tacrolimus in DDKT recipients treated with thymoglobulin resulted in better allograft function during the only early post-transplant period compared to early initiation. However, delayed tacrolimus initiation was associated with higher rates of acute rejection and reduced graft survival. Therefore, early use of tacrolimus in patients with thymoglobulin may have a positive effect on the clinical outcomes of DDKT recipients. Funding: Government Support – Non-U.S.