Personalized dosing protocol for extended-release tacrolimus in kidney transplant recipients in the early postoperative period

Abstract

Objective: to develop a personalized algorithm for extended-release tacrolimus in kidney recipients and to analyze its early outcomes in comparison with a retrospective control group.Materials and methods. The first (I) control group «Standard Protocol» included 228 patients operated on at Botkin City Clinical Hospital from June 2018 to November 2021; tacrolimus was administered postoperatively in a starting standard dosage of 0.2 mg/kg. The second group (II) consisted of 75 patients operated from December 2021 to November 2022, whose postoperative treatment involved a personalized extended-release tacrolimus dosing protocol. Induction immunosuppression was similar in both groups. The target tacrolimus level in the early postoperative period was considered to be 10-12 ng/ml for all patients. The comparison criteria included incidence of Over-immunosuppression (tacrolimus C0 >15 ng/ml), incidence of acute rejection and infectious complications in the first month after surgery, incidence and duration of delayed graft function (DGF), and length of stay at the hospital.Results. Over-immunosuppression was statistically significantly lower in the personalized protocol group, with 36.7% in group I and 87.5% in group II (p < 0.001). There was also a lower incidence of early infectious complications in group II: 5.4% vs. 13.2%, however, without reaching a level of statistical significance (p = 0.088). DGF incidence in group I and group II were 25.4% (58/228) and 22.7% (17/75), respectively. The length of stay at the hospital in group II was also statistically significantly lower: 13 versus 19 bed days (p = 0.033). In both subgroups, no patient developed acute rejection in the first month after surgery (p = 1).Conclusion. The personalized dosing protocol that was developed for extended-release tacrolimus in kidney recipients achieves the target levels of the drug recommended for the early postoperative period with low risk of under-immunosuppression and associated acute graft rejection, with a significantly lower incidence of over-immunosuppression.