Monitoring intracellular tacrolimus concentrations and its relationship with rejection in the early phase after renal transplantation.

INTRODUCTION

After kidney transplantation, rejection and drug-related toxicity occur despite tacrolimus whole-blood pre-dose concentrations ([Tac]) being within the target range. The tacrolimus concentration within peripheral blood mononuclear cells ([Tac]) might correlate better with clinical outcomes. The aim of this study was to investigate the correlation between [Tac] and [Tac] the evolution of [Tac] and the [Tac]/[Tac] ratio, and to assess the relationship between tacrolimus concentrations and the occurrence of rejection.

METHODS

In this prospective study, samples for the measurement of [Tac] and [Tac] were collected on days 3 and 10 after kidney transplantation, and on the morning of a for-cause kidney transplant biopsy. Biopsies were reviewed according to the Banff 2019 update.

RESULTS

Eighty-three [Tac] samples were measured of 44 kidney transplant recipients. The correlation between [Tac] and [Tac] was poor (Pearson's r = 0.56 (day 3); r = 0.20 (day 10)). Both the dose-corrected [Tac] and the [Tac]/[Tac] ratio were not significantly different between days 3 and 10, and the median inter-occasion variability of the dose-corrected [Tac] and the [Tac]/[Tac] ratio were 19.4% and 23.4%, respectively (n = 24). Neither [Tac] [Tac] nor the [Tac]/[Tac] ratio were significantly different between patients with biopsy-proven acute rejection (n = 4) and patients with acute tubular necrosis (n = 4) or a cancelled biopsy (n = 9; p > 0.05).

CONCLUSION

Tacrolimus exposure and distribution appeared stable in the early phase after transplantation. [Tac] was not significantly associated with the occurrence of rejection. A possible explanation for these results might be related to the low number of patients included in this study and also due to the fact that PBMCs are not a specific enough matrix to monitor tacrolimus concentrations.