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

doi:10.1016/j.clinbiochem.2021.12.002

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

Leiden University Medical Centre

Research output: Contribution to journal › Article › Academic › peer-review

17 Citations (Scopus)

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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 language	English
Pages (from-to)	9-15
Number of pages	7
Journal	Clinical Biochemistry
Volume	101
DOIs	https://doi.org/10.1016/j.clinbiochem.2021.12.002
Publication status	Published - Mar 2022

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10.1016/j.clinbiochem.2021.12.002

1-s2.0-S0009912021003192-mainFinal published version, 609 KBLicence: CC BY

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Francke, M. I., Andrews, L. M., Lan Le, H., van de Velde, D., Dieterich, M., Udomkarnjananun, S., Clahsen-van Groningen, M. C., Baan, C. C., van Gelder, T., de Winter, B. C. M., & Hesselink, D. A. (2022). Monitoring intracellular tacrolimus concentrations and its relationship with rejection in the early phase after renal transplantation. Clinical Biochemistry, 101, 9-15. https://doi.org/10.1016/j.clinbiochem.2021.12.002

@article{dc4135b095834e4fbf591db1f2ab91da,

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2022",

month = mar,

doi = "10.1016/j.clinbiochem.2021.12.002",

language = "English",

volume = "101",

pages = "9--15",

journal = "Clinical Biochemistry",

issn = "0009-9120",

publisher = "Elsevier Inc.",

}

Francke, MI, Andrews, LM, Lan Le, H, van de Velde, D, Dieterich, M, Udomkarnjananun, S, Clahsen-van Groningen, MC , Baan, CC, van Gelder, T, de Winter, BCM & Hesselink, DA 2022, 'Monitoring intracellular tacrolimus concentrations and its relationship with rejection in the early phase after renal transplantation', Clinical Biochemistry, vol. 101, pp. 9-15. https://doi.org/10.1016/j.clinbiochem.2021.12.002

TY - JOUR

T1 - Monitoring intracellular tacrolimus concentrations and its relationship with rejection in the early phase after renal transplantation

AU - Francke, Marith I.

AU - Andrews, Louise M.

AU - Lan Le, Hoang

AU - van de Velde, Daan

AU - Dieterich, Marjolein

AU - Udomkarnjananun, Suwasin

AU - Clahsen-van Groningen, Marian C.

AU - Baan, Carla C.

AU - van Gelder, Teun

AU - de Winter, Brenda C.M.

AU - Hesselink, Dennis A.

PY - 2022/3

Y1 - 2022/3

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85121275281

U2 - 10.1016/j.clinbiochem.2021.12.002

DO - 10.1016/j.clinbiochem.2021.12.002

M3 - Article

C2 - 34890583

AN - SCOPUS:85121275281

SN - 0009-9120

VL - 101

SP - 9

EP - 15

JO - Clinical Biochemistry

JF - Clinical Biochemistry

ER -

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

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