Leiden University Scholarly Publications

Francke, M.I.; Andrews, L.M.; H.L. le; Velde, D. van de; Dieterich, M.; Udomkarnjananun, S.; ... ; Hesselink, D.A. 2022

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

Article / Letter to editor

open access

Introduction: After kidney transplantation, rejection and drug-related toxicity occur despite tacrolimus whole blood pre-dose concentrations ([Tac](blood)) being within the target range. The... Show moreIntroduction: After kidney transplantation, rejection and drug-related toxicity occur despite tacrolimus whole blood pre-dose concentrations ([Tac](blood)) being within the target range. The tacrolimus concentration within peripheral blood mononuclear cells ([Tac](cells)) might correlate better with clinical outcomes. The aim of this study was to investigate the correlation between [Tac](blood) and [Tac](cells), the evolution of [Tac](cells) and the [Tac](cells)/[Tac](blood) 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](blood) and [Tac](cells) 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](cells) samples were measured of 44 kidney transplant recipients. The correlation between [Tac](cells) and [Tac](blood) was poor (Pearson's r = 0.56 (day 3); r = 0.20 (day 10)). Both the dose-corrected [Tac](cells) and the [Tac](cells)/[Tac](blood) ratio were not significantly different between days 3 and 10, and the median inter-occasion variability of the dose-corrected [Tac](cells) and the [Tac](cells)/[Tac](blood) ratio were 19.4% and 23.4%, respectively (n = 24). Neither [Tac](cells), [Tac](blood), nor the [Tac](cells)/[Tac](blood) 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](cells) 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. Show less