Early Monitoring and Subsequent Gain of Tacrolimus Time-In-Therapeutic Range May Improve Clinical Outcomes After Living Kidney Transplantation

Background The early identification of recipients at high risk of graft loss is clinically relevant after kidney transplantation. The authors explored whether the earlier monitoring of tacrolimus (Tac) time-in-therapeutic range (TTR) is predictive of and a subsequent gain in TTR improves transplant outcomes. Methods The TTR within 3, 6, 9, and 12 months was evaluated. Multivariate Cox analyses were performed to explore when TTR was predictive of transplant outcomes. Patients were divided into 3 groups based on incremental TTR change [TTR gain (increase >10%), TTR stable (maintained within 10%), and TTR loss (decrease >10%)] and 4 groups based on predefined cutoff values [low-low (LL), low-high (LH), high-low (HL), and high-high (HH)] using 6- and 12-month TTRs. Death-censored graft loss and patient death were primary outcomes. Results Nonlinear associations were observed between 6-, 9-, and 12-month TTR and death-censored graft and patient survival rates. In multivariate analysis, every 10% increase in 6-, 9-, and 12-month TTRs was associated with reduced patient death [hazard ratio (HR): 0.83; HR: 0.68; HR: 0.61, respectively] and graft loss (HR: 0.88; HR: 0.73; HR: 0.66, respectively). A nonlinear relationship was observed between transplant outcomes and incremental changes in TTR. TTR gain and stable TTR contributed to higher graft survival (HR: 0.20; HR: 0.21) and patient survival (HR: 0.14; HR: 0.15) rates than TTR loss, whereas the former 2 had comparable outcomes. Furthermore, compared with those in the HH group, the LL and HL groups had inferior graft survival (HR: 3.33; HR: 5.17) and patient survival (HR: 5.15; HR: 8.94) rates, whereas the LH group had similar outcomes (P = 0.63, P = 0.97). Nonadherence was the main controllable risk factor for low TTR. Conclusions The 6-month TTR identified patients at higher risk of worse outcomes. The subsequent gain of TTR may contribute to better transplant outcomes.