{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:43:58Z","timestamp":1791924238728,"version":"4.3.4"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:p>\n                    AKI is a rare but life-threatening complication of the administration of methotrexate (MTX) at high doses (\u22651 g\/m\n                    <jats:sup>2<\/jats:sup>\n                    ) for the treatment of solid or hematological malignancies. MTX overexposure can lead to MTX-AKI and subsequent higher risk of extrakidney toxicities, morbidity, and mortality. MTX-AKI can also lead to secondary CKD requiring a reduced dose or contraindication for subsequent MTX infusions, thus worsening the cancer-related prognosis. Treatment of MTX-AKI is mainly preventive, combining alkaline hyperhydration, withdrawal of all nephrotoxic agents and drugs that modulate the metabolism of MTX, metabolic salvage using leucovorin (folinic acid), and close monitoring of serum MTX and creatinine concentrations. Glucarpidase (carboxypeptidase-G2), a recombinant bacterial enzyme that hydrolyzes MTX into two noncytotoxic metabolites, should be considered for patients with MTX overexposure to prevent and lessen AKI and other potential toxicities. This article provides a comprehensive review of MTX metabolism, mechanisms and prevention of MTX-AKI, and its management.\n                  <\/jats:p>","DOI":"10.34067\/kid.0000000725","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T12:04:45Z","timestamp":1738325085000},"page":"476-481","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":13,"title":["Prevention and Treatment of Acute Kidney Injury Associated with High-Dose Methotrexate"],"prefix":"10.34067","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-0927","authenticated-orcid":false,"given":"Stanislas","family":"Faguer","sequence":"first","affiliation":[{"name":"Department of Nephrology and Organ Transplantation, French Intensive Care Renal Network (F.I.R.N), University Hospital of Toulouse, Toulouse, France"},{"name":"Faculty of Health, University of Toulouse-3, Toulouse, France"},{"name":"Renal Fibrosis Lab, INSERM UMR1297, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00e9","family":"Medrano","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Organ Transplantation, French Intensive Care Renal Network (F.I.R.N), University Hospital of Toulouse, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Tavitian","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncopole \u2013 Cancer Institute of Toulouse, University Hospital of Toulouse, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Oberic","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncopole \u2013 Cancer Institute of Toulouse, University Hospital of Toulouse, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"issue":"10","key":"B1-20250327","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1002\/cncr.20255","article-title":"High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma: incidence, treatment, and outcome","volume":"100","author":"Widemann","year":"2004","journal-title":"Cancer."},{"issue":"2","key":"B2-20250327","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/leu.2009.251","article-title":"Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia","volume":"24","author":"Schmiegelow","year":"2010","journal-title":"Leukemia."},{"issue":"12","key":"B3-20250327","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1634\/theoncologist.2015-0164","article-title":"Preventing and managing toxicities of high-dose 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