Early therapeutic drug monitoring of methotrexate and its association with acute kidney injury: A retrospective cohort study
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 use...
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Wiley
2024-09-01
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| Online Access: | https://doi.org/10.1002/cam4.70176 |
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| author | Nicolás Tentoni Miriam Hwang Gabriela Villanueva Ryan Combs Jennifer Lowe Laura B. Ramsey Zachary L. Taylor Thais Murciano Carrillo María Dolores Aumente Teresa López‐Viñau López Carmelo Rizzari Scott C. Howard |
| author_facet | Nicolás Tentoni Miriam Hwang Gabriela Villanueva Ryan Combs Jennifer Lowe Laura B. Ramsey Zachary L. Taylor Thais Murciano Carrillo María Dolores Aumente Teresa López‐Viñau López Carmelo Rizzari Scott C. Howard |
| author_sort | Nicolás Tentoni |
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| description | 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. |
| format | Article |
| id | doaj-art-e36aebfabb7e428d82a45f18aff48572 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-e36aebfabb7e428d82a45f18aff485722025-02-07T09:08:08ZengWileyCancer Medicine2045-76342024-09-011317n/an/a10.1002/cam4.70176Early therapeutic drug monitoring of methotrexate and its association with acute kidney injury: A retrospective cohort studyNicolás Tentoni0Miriam Hwang1Gabriela Villanueva2Ryan Combs3Jennifer Lowe4Laura B. Ramsey5Zachary L. Taylor6Thais Murciano Carrillo7María Dolores Aumente8Teresa López‐Viñau López9Carmelo Rizzari10Scott C. Howard11Laboratory of Applied Statistics in the Health Sciences, School of Medicine University of Buenos Aires Buenos Aires ArgentinaResonance Memphis Tennessee USAResonance Memphis Tennessee USAResonance Memphis Tennessee USAResonance Memphis Tennessee USADivision of Clinical Pharmacology, Toxicology & Therapeutic Innovation Children's Mercy Hospital Kansas City Missouri USADivision of Translational and Clinical Pharmacology Cincinnati Children's Hospital Medical Center Cincinnati Ohio USAPediatric Oncology and Hematology Service Vall d'Hebron University Hospital Barcelona SpainPharmacy Service Reina Sofía University Hospital/Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba Córdoba SpainPharmacy Service Reina Sofía University Hospital/Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba Córdoba SpainDepartment of Pediatrics, Pediatric Hematology Oncology Unit University of Milano‐Bicocca, IRCCS San Gerardo dei Tintori Monza ItalyResonance Memphis Tennessee USAAbstract 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.https://doi.org/10.1002/cam4.70176acute kidney injurybiomarkerearly methotrexate elimination half‐lifehigh‐dose methotrexate |
| spellingShingle | Nicolás Tentoni Miriam Hwang Gabriela Villanueva Ryan Combs Jennifer Lowe Laura B. Ramsey Zachary L. Taylor Thais Murciano Carrillo María Dolores Aumente Teresa López‐Viñau López Carmelo Rizzari Scott C. Howard Early therapeutic drug monitoring of methotrexate and its association with acute kidney injury: A retrospective cohort study Cancer Medicine acute kidney injury biomarker early methotrexate elimination half‐life high‐dose methotrexate |
| title | Early therapeutic drug monitoring of methotrexate and its association with acute kidney injury: A retrospective cohort study |
| title_full | Early therapeutic drug monitoring of methotrexate and its association with acute kidney injury: A retrospective cohort study |
| title_fullStr | Early therapeutic drug monitoring of methotrexate and its association with acute kidney injury: A retrospective cohort study |
| title_full_unstemmed | Early therapeutic drug monitoring of methotrexate and its association with acute kidney injury: A retrospective cohort study |
| title_short | Early therapeutic drug monitoring of methotrexate and its association with acute kidney injury: A retrospective cohort study |
| title_sort | early therapeutic drug monitoring of methotrexate and its association with acute kidney injury a retrospective cohort study |
| topic | acute kidney injury biomarker early methotrexate elimination half‐life high‐dose methotrexate |
| url | https://doi.org/10.1002/cam4.70176 |
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