Optimization of the Tacrolimus Concentration-to-Dose Ratio Cut-Off Value to Define Metabolism Groups

TL;DR

This study finds the best cut-off value for a drug ratio to predict kidney function outcomes in transplant patients.

Contribution

The study identifies an optimized tacrolimus concentration-to-dose ratio cut-off for defining metabolism groups.

Findings

A C/D ratio of 0.94 optimally differentiates fast and slow tacrolimus metabolizers for renal function development.

A cut-off of 1.0 is suggested for clinical use due to its simplicity and proximity to the optimal value.

Fast metabolism is linked to impaired kidney function after transplantation.

Abstract

Background/Objectives: The tacrolimus (Tac) concentration-to-dose ratio (C/D ratio) has been described as a predictive marker for several outcome parameters after renal transplantation (RTx). Different C/D ratio values are used to define fast (low C/D ratio) and slow Tac metabolizers (high C/D ratio). In this study, the R package was used to determine the optimal C/D ratio cut-off value to define the Tac metabolism type with a high predictive value for the development of renal function. Methods: The data of 389 RTx patients who received an initial immunosuppression with immediate-release tacrolimus (IR-Tac), mycophenolate, prednisolone, and an induction with basiliximab were analyzed. The Tac C/D ratio (ng/mL × 1/mg) of all patients was calculated 3 months after RTx and the maximally selected Wilcoxon statistic was applied to determine the optimal C/D ratio cut-off value for renal function development over a 5-year follow-up. Results: A C/D ratio of 0.94 provided the optimal differentiation between fast and slow Tac metabolism in relation to renal function development at 1, 2, 3, and 4 years of follow-up, and at 0.95 five years after RTx. Conclusions: As fast Tac metabolism is associated with the development of an impaired renal function, it is essential to identify patients at risk early after RTx. In order to keep the application simple for clinical routine, we suggest calculating the C/D ratio 3 months after RTx and using 1.0 (≤1.0 = fast metabolizer) as the cut-off, which is very close to the optimal value.

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