Background: The tacrolimus concentration-to-dose (C/D) ratio is valuable for optimizing nephrotoxicity-related renal outcomes. Prospective data on the C/D ratio in kidney transplant recipients newly treated with MeltDose tacrolimus are limited. We analyzed the C/D ratio pattern of MeltDose tacrolimus and its effect on posttransplant renal function, comparing it with the literature data on immediate-release tacrolimus (IR-Tac). Methods: In total, 101 adult kidney transplant recipients on a standard immunosuppressive regimen including MeltDose tacrolimus were enrolled in this prospective, multicenter cohort study and followed for 12 months. The C/D ratio classified patients as fast, intermediate, or slow metabolizers. Renal function was assessed via the estimated glomerular filtration rate (eGFR). MeltDose tacrolimus data were compared with previous IR-Tac data by bootstrapping. Results: The cohort exhibited a right-skewed C/D ratio distribution with a mean of 2.12 ng/mL × 1/mg, which was significantly greater than the 1.29 mean for IR-Tac (p < 0.001). Compared with fast metabolizers, slow metabolizers of MeltDose tacrolimus experienced greater eGFR gains at 6 months post-transplantation (median +7.9 vs. -3.6 mL/min; p = 0.005). A Bayesian linear mixed-effects model predicting the eGFR at month 12 identified the baseline eGFR, time from transplant, body mass index, and log-transformed C/D ratio as significant variables. A one-unit increase in the log-transformed C/D ratio corresponded to an approximate increase of 4.5 mL/min in the eGFR at month 12. Conclusions: Slow metabolizers of MeltDose tacrolimus had significantly better renal function outcomes than fast metabolizers. MeltDose tacrolimus is associated with slower metabolism than is IR-Tac, as evidenced by its higher C/D ratios.
Keywords: C/D ratio; LCPT; MeltDose; glomerular filtration rate; kidney transplantation; pharmacokinetics; tacrolimus.