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

Marith I. Francke*, Louise M. Andrews, Hoang Lan Le, Daan van de Velde, Marjolein Dieterich, Suwasin Udomkarnjananun, Marian C. Clahsen-van Groningen, Carla C. Baan, Teun van Gelder, Brenda C.M. de Winter, Dennis A. Hesselink

*Corresponding author for this work

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Abstract

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 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.

Original languageEnglish
Pages (from-to)9-15
Number of pages7
JournalClinical Biochemistry
Volume101
DOIs
Publication statusPublished - Mar 2022

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