*Purpose: Tacrolimus (Tac) remains the cornerstone of kidney transplantation immunosuppression. Its narrow therapeutic index demands therapeutic drug monitoring. The C/D ratio (Tac trough concentration / daily Tac dose) was shown to be associated with Tac nephrotoxicity and early acute rejection. We herein investigated the value of the C/D ratio in predicting graft survival.

*Methods: We retrospectively analyzed the cohort of Tac-treated kidney transplant recipient (KTr) between 2004 and mid-2018 at Grenoble University Hospital. We computed the median C/D ratio (medCDr) over time and separated fast metabolizers (C/D ratio < 1.05) from normal or slow metabolizers (C/D ratio ≥ 1.05). Using a multivariate Cox proportional hazard model, adjusting for the median C/D ratio, development of de novo Donor Specific Antibodies (dnDSA), body mass index (BMI), mean Tac trough levels and standard deviation of the Tac trough levels, we assessed whether the C/D ratio was a predictor of death-censored graft survival.

*Results: A total of 1011 KTr were included in the analysis. The mean Tac trough level was 6.65 µg/l, with an overall mean Tac dose of 3.33mg/day. Virtually all patients received Tac+Mycophenolate, with a usual Tac trough targeted range from 5 to 8 µg/l. The mean medCDr was 2.19, ranging from 0.24 to 8.57. 141 KTr had a medCDr<1.05. There were 92 death-censored graft losses, (23 in the fast metabolizer group). In the multivariate Cox model, the hazard ratio associated with the medCDr was 3.07 (p<.001), independently from dnDSA development (HR 2.79, p<.001) and mean Tac trough levels (HR 1.5, p<.001). Other factors were not significantly associated with KTr survival. As shown in figure 1, the survival difference reached 10% after 4 years and remained stable thereafter.

*Conclusions: Tacrolimus metabolization, as defined by the C/D ratio, independently impacts KTr death-censored graft survival.

« Back to 2019 American Transplant Congress