Document Type

Article

Publication Date

9-2024

Identifier

DOI: 10.1002/cam4.70176; PMCID: PMC11386298

Abstract

INTRODUCTION: High-dose methotrexate (HDMTX) use can be limited by the development of acute kidney injury (AKI). Early AKI detection is paramount to prevent further renal injury and irreversible toxicities. This study sought to determine whether early elimination patterns of MTX would be useful as a biomarker of AKI in HDMTX treatment.

METHODS: This retrospective cohort study included two sites that collected ≥2 MTX levels within 16 h from completion of MTX infusion. Early levels were tagged and MTX elimination half-life (t½) were calculated from combinations of two of three different early time periods. Receiver operating characteristic (ROC) curves were synthesized for each elimination t½ (biomarker) with respect to AKI and delayed methotrexate elimination (DME); the biomarker with the highest area under the ROC curve (AUC) was tested in a multiple variable logistic regression model.

RESULTS: Data from 169 patients who received a total of 556 courses of HDMTX were analyzed. ROC analysis revealed MTX elimination t½ calculated from the second and third time periods had the highest AUC for AKI at 0.62 (interquartile range [IQR] 0.56-0.69) and DME at 0.86 (IQR 0.73-1.00). After adjusting for age, sex, dose (mg/m2), infusion duration, HDMTX course, and baseline estimated glomerular filtration rate, it remained significant for AKI with an OR of 1.29 and 95% confidence interval of 1.03-1.65.

CONCLUSION: Early MTX elimination t½ measured within 16 h of infusion completion was significantly associated with the development of AKI and serves as an early clearance biomarker that may identify patients who benefit from increased hydration, augmented leucovorin rescue, and glucarpidase administration.

Journal Title

Cancer Med

Volume

13

Issue

17

First Page

70176

Last Page

70176

MeSH Keywords

Humans; Acute Kidney Injury; Methotrexate; Female; Male; Retrospective Studies; Middle Aged; Drug Monitoring; Aged; ROC Curve; Antimetabolites, Antineoplastic; Biomarkers; Adult

Keywords

acute kidney injury; biomarker; early methotrexate elimination half‐life; high‐dose methotrexate

Comments

Grants and funding

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Publisher's Link: https://onlinelibrary.wiley.com/doi/10.1002/cam4.70176

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