2026-04-13T04:17:23Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/122732025-10-24T10:24:37Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Tentoni, Nicolás
author
HWANG, MIRIAM
author
Villanueva, Gabriela
author
Combs, Ryan
author
Lowe, Jennifer
author
Ramsey, Laura
author
Murciano, Thais
2025-10-24T10:24:37Z
2025-10-24T10:24:37Z
2024-11-25T13:56:44Z2024-11-25T13:56:44Z2024-09
http://hdl.handle.net/11351/12273
Acute kidney injury; Biomarker; High‐dose methotrexateLesión renal aguda; Biomarcador; Metotrexato en dosis altasLesió renal aguda; Biomarcador; Metotrexat en dosis altesIntroduction
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.BTG Pharmaceuticals
Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
Antimetabòlits - Ús terapèutic - Efectes secundaris
Insuficiència renal aguda - Diagnòstic
Medicaments - Monitoratge
DISEASES::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Acute Kidney Injury
Other subheadings::Other subheadings::Other subheadings::/chemically induced
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Antimetabolites::Antimetabolites, Antineoplastic
Other subheadings::Other subheadings::Other subheadings::/adverse effects
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Diagnostic Techniques and Procedures::Monitoring, Physiologic::Drug Monitoring
ENFERMEDADES::enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::insuficiencia renal::lesión renal aguda
Otros calificadores::Otros calificadores::Otros calificadores::/inducido químicamente
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::antimetabolitos::antimetabolitos antineoplásicos
Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::técnicas y procedimientos diagnósticos::monitorización fisiológica::monitorización de medicamentos
Early therapeutic drug monitoring of methotrexate and its association with acute kidney injury: A retrospective cohort study
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion