2026-04-17T14:59:58Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/122732025-10-24T10:24:37Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Tentoni, Nicolás author HWANG, MIRIAM author Villanueva, Gabriela author Combs, Ryan author Lowe, Jennifer author Ramsey, Laura author Murciano, Thais author 2024-11-25T13:56:44Z 2024-11-25T13:56:44Z 2024-09 Acute kidney injury; Biomarker; High‐dose methotrexate Lesión renal aguda; Biomarcador; Metotrexato en dosis altas Lesió renal aguda; Biomarcador; Metotrexat en dosis altes 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. BTG Pharmaceuticals http://hdl.handle.net/11351/12273 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