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Plasma metabolomic profiling reveals factors associated with dose-adjusted trough concentration of tacrolimus in liver transplant recipients

Inter- and intrapatient variability of tacrolimus exposure is a vital prognostic risk factor for the clinical outcome of liver transplantation. New factors or biomarkers characterizing tacrolimus disposition is essential for optimal dose prediction in recipients of liver transplant. The aim of the s...

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Autores principales: Zhu, Huaijun, Wang, Min, Xiong, Xiaofu, Du, Yao, Li, Danying, Wang, Zhou, Ge, Weihong, Zhu, Yizhun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9659571/
https://www.ncbi.nlm.nih.gov/pubmed/36386159
http://dx.doi.org/10.3389/fphar.2022.1045843
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author Zhu, Huaijun
Wang, Min
Xiong, Xiaofu
Du, Yao
Li, Danying
Wang, Zhou
Ge, Weihong
Zhu, Yizhun
author_facet Zhu, Huaijun
Wang, Min
Xiong, Xiaofu
Du, Yao
Li, Danying
Wang, Zhou
Ge, Weihong
Zhu, Yizhun
author_sort Zhu, Huaijun
collection PubMed
description Inter- and intrapatient variability of tacrolimus exposure is a vital prognostic risk factor for the clinical outcome of liver transplantation. New factors or biomarkers characterizing tacrolimus disposition is essential for optimal dose prediction in recipients of liver transplant. The aim of the study was to identify potential plasma metabolites associated with the dose-adjusted trough concentration of tacrolimus in liver transplant recipients by using a global metabolomic approach. A total of 693 plasma samples were collected from 137 liver transplant recipients receiving tacrolimus and regular therapeutic drug monitoring. Untargeted metabolomic analysis was performed by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. Univariate and multivariate analyses with a mixed linear model were conducted, and the results showed that the dose-adjusted tacrolimus trough concentration was associated with 31 endogenous metabolites, including medium- and long-chain acylcarnitines such as stearoylcarnitine (β = 0.222, p = 0.001), microbiota-derived uremic retention solutes such as indolelactic acid (β = 0.194, p = 0.007), bile acids such as taurohyodeoxycholic acid (β = −0.056, p = 0.002), and steroid hormones such as testosterone (β = 0.099, p = 0.001). A multiple linear mixed model including 11 metabolites and clinical information was established with a suitable predictive performance (correlation coefficient based on fixed effects = 0.64 and correlation coefficient based on fixed and random effects = 0.78). These data demonstrated that microbiota-derived uremic retention solutes, bile acids, steroid hormones, and medium- and long-chain acylcarnitines were the main metabolites associated with the dose-adjusted trough concentration of tacrolimus in liver transplant recipients.
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spelling pubmed-96595712022-11-15 Plasma metabolomic profiling reveals factors associated with dose-adjusted trough concentration of tacrolimus in liver transplant recipients Zhu, Huaijun Wang, Min Xiong, Xiaofu Du, Yao Li, Danying Wang, Zhou Ge, Weihong Zhu, Yizhun Front Pharmacol Pharmacology Inter- and intrapatient variability of tacrolimus exposure is a vital prognostic risk factor for the clinical outcome of liver transplantation. New factors or biomarkers characterizing tacrolimus disposition is essential for optimal dose prediction in recipients of liver transplant. The aim of the study was to identify potential plasma metabolites associated with the dose-adjusted trough concentration of tacrolimus in liver transplant recipients by using a global metabolomic approach. A total of 693 plasma samples were collected from 137 liver transplant recipients receiving tacrolimus and regular therapeutic drug monitoring. Untargeted metabolomic analysis was performed by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. Univariate and multivariate analyses with a mixed linear model were conducted, and the results showed that the dose-adjusted tacrolimus trough concentration was associated with 31 endogenous metabolites, including medium- and long-chain acylcarnitines such as stearoylcarnitine (β = 0.222, p = 0.001), microbiota-derived uremic retention solutes such as indolelactic acid (β = 0.194, p = 0.007), bile acids such as taurohyodeoxycholic acid (β = −0.056, p = 0.002), and steroid hormones such as testosterone (β = 0.099, p = 0.001). A multiple linear mixed model including 11 metabolites and clinical information was established with a suitable predictive performance (correlation coefficient based on fixed effects = 0.64 and correlation coefficient based on fixed and random effects = 0.78). These data demonstrated that microbiota-derived uremic retention solutes, bile acids, steroid hormones, and medium- and long-chain acylcarnitines were the main metabolites associated with the dose-adjusted trough concentration of tacrolimus in liver transplant recipients. Frontiers Media S.A. 2022-10-31 /pmc/articles/PMC9659571/ /pubmed/36386159 http://dx.doi.org/10.3389/fphar.2022.1045843 Text en Copyright © 2022 Zhu, Wang, Xiong, Du, Li, Wang, Ge and Zhu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhu, Huaijun
Wang, Min
Xiong, Xiaofu
Du, Yao
Li, Danying
Wang, Zhou
Ge, Weihong
Zhu, Yizhun
Plasma metabolomic profiling reveals factors associated with dose-adjusted trough concentration of tacrolimus in liver transplant recipients
title Plasma metabolomic profiling reveals factors associated with dose-adjusted trough concentration of tacrolimus in liver transplant recipients
title_full Plasma metabolomic profiling reveals factors associated with dose-adjusted trough concentration of tacrolimus in liver transplant recipients
title_fullStr Plasma metabolomic profiling reveals factors associated with dose-adjusted trough concentration of tacrolimus in liver transplant recipients
title_full_unstemmed Plasma metabolomic profiling reveals factors associated with dose-adjusted trough concentration of tacrolimus in liver transplant recipients
title_short Plasma metabolomic profiling reveals factors associated with dose-adjusted trough concentration of tacrolimus in liver transplant recipients
title_sort plasma metabolomic profiling reveals factors associated with dose-adjusted trough concentration of tacrolimus in liver transplant recipients
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9659571/
https://www.ncbi.nlm.nih.gov/pubmed/36386159
http://dx.doi.org/10.3389/fphar.2022.1045843
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