*Purpose: There is emerging interest in the concentration-to-dose (C/D) ratio of tacrolimus (Tac) as it is linked to outcomes after renal transplantation (RTx). Recently, we were able to classify patients into two major Tac metabolism groups by calculating the C/D ratio (expressed as the Tac blood concentration normalized by the daily dose). A cut-off of 1.05 µg/L x 1/mg three months after RTx in stable patients allows for risk stratification into slow (≥1.05) and fast (<1.05) metabolizers, the latter being at increased risk of calcineurin-inhibitor nephrotoxicity, as well as lower eGFR and decreased five-year patient and graft survival. Classification of patients based on the 3-month C/D ratio proved to be stable over time beyond the third postoperative month. To identify patients who may profit from a modification of the immunosuppressive regime as early as possible, we questioned if the C/D ratio can be reliably calculated within the first days after RTx.

*Methods: We retrospectively analyzed 882 patients who received a donor kidney at the University Hospital Münster between January 2007 and December 2017. The C/D ratio was calculated for each of the first ten postoperative days in cases of available Tac trough level and dosage data and used to categorize patients. C/D ratio cut-off values were calculated for each day based on ROC curve analysis and identification of the Youden-index maximum.

*Results: We found a C/D ratio of 0.87 on the third day after RTx to allow the best prediction (in comparison to all other postoperative days) of the 3-month Tac metabolism type (AUC = 0.741; p < 0.001). However, using this cut-off, the outcomes of slow and fast metabolizers, including patient and graft survival, acute rejections and incidence of delayed graft function, were comparable showing the absent discriminative power of the early C/D ratios after RTx.

*Conclusions: While the C/D ratio calculated three months after RTx is a simple and valuable tool for risk stratification of patients with impaired outcome after RTx, the C/D ratio calculation within the first ten days does not predict neither the long-term metabolism type nor the outcome after RTx. Tac clearance is (too) strongly influenced by the posttransplant day which finds its reasoning in e.g. changes in gastrointestinal mobility, albumin, hematocrit, and steroid dosing. Further studies should evaluate whether combined C/D ratios of more than one day or at later time points provide better performance.

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