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Identification of urinary metabolites correlated with tacrolimus levels through high-precision liquid chromatography-mass spectrometry and machine learning algorithms in kidney transplant patients.

Authors :
Burghelea D
Moisoiu T
Ivan C
Elec A
Munteanu A
Tabrea R
Antal O
Kacso TP
Socaciu C
Elec FI
Kacso IM
Source :
Medicine and pharmacy reports [Med Pharm Rep] 2025 Jan; Vol. 98 (1), pp. 125-134. Date of Electronic Publication: 2025 Jan 31.
Publication Year :
2025

Abstract

Background and Aim: Tacrolimus, a widely used immunosuppressive drug in kidney transplant recipients, exhibits a narrow therapeutic window necessitating careful monitoring of its concentration to balance efficacy and minimize dose-related toxic effects. Although essential, this approach is not optimal, and tacrolinemia, even in the therapeutic interval, might be associated with toxicity and rejection within range. This study aimed to identify specific urinary metabolites associated with tacrolimus levels in kidney transplant patients using a combination of serum high-precision liquid chromatography-mass spectrometry (HPLC-MS) and machine learning algorithms.<br />Methods: A cohort of 42 kidney transplant patients, comprising 19 individuals with high tacrolimus levels (>8 ng/mL) and 23 individuals with low tacrolimus levels (<5 ng/mL), were included in the analysis. Urinary samples were subjected to HPLC-MS analysis, enabling comprehensive metabolite profiling across the study cohort. Additionally, tacrolimus concentrations were quantified using established clinical assays.<br />Results: Through an extensive analysis of the HPLC-MS data, a panel of five metabolites were identified that exhibited a significant correlation with tacrolimus levels (Valeryl carnitine, Glycyl-tyrosine, Adrenosterone, LPC 18:3 and 6-methylprednisolone). Machine learning algorithms were then employed to develop a predictive model utilizing the identified metabolites as features. The logistic regression model achieved an area under the curve of 0.810, indicating good discriminatory power and classification accuracy of 0.690.<br />Conclusions: This study demonstrates the potential of integrating HPLC-MS metabolomics with machine learning algorithms to identify urinary metabolites associated with tacrolimus levels. The identified metabolites are promising biomarkers for monitoring tacrolimus therapy, aiding in dose optimization and personalized treatment approaches.

Details

Language :
English
ISSN :
2668-0572
Volume :
98
Issue :
1
Database :
MEDLINE
Journal :
Medicine and pharmacy reports
Publication Type :
Academic Journal
Accession number :
39949902
Full Text :
https://doi.org/10.15386/mpr-2805