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Although low\u2010dose MTX (5\u201320\u2009mg\/week) is generally considered safe, it has a narrow therapeutic index, and toxicity can occur even at therapeutic doses, particularly in high\u2010risk patients. We describe a 58\u2009year\u2010old man with RA and chronic kidney disease (CKD) who presented with gastrointestinal symptoms, neurologic impairment, and a papulopustular rash. Laboratory evaluation revealed pancytopenia and acute kidney injury (AKI) superimposed on CKD. Despite a normal serum MTX level, clinical findings strongly suggested MTX toxicity. The patient received emergent hemodialysis, leucovorin rescue therapy, hematologic support, and intensive care management. Extensive investigations excluded alternative hematologic, infectious, and systemic causes. His clinical course was complicated by acute pancreatitis, and he ultimately died. This case emphasizes that serum MTX levels may not reliably predict toxicity in high\u2010risk patients and underscores the importance of recognizing clinical signs and symptoms, promptly identifying early manifestations, discontinuing MTX, and initiating leucovorin rescue therapy.<\/jats:p>","DOI":"10.1002\/ccr3.72898","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T07:31:53Z","timestamp":1781249513000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Methotrexate Toxicity in a Patient With Renal Failure Despite a Normal Methotrexate Concentration: A Case Report and Literature Review"],"prefix":"10.1002","volume":"14","author":[{"given":"Fatemeh","family":"Afra","sequence":"first","affiliation":[{"name":"Clinical Pharmacy Department, Sina Hospital Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahshad","family":"Ghoddusi","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Sina Hospital Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Mottahedi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Sina Hospital Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Albaji","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Disease, Sina Hospital Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Kafan","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Disease, Sina Hospital Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roya","family":"Saedpanah","sequence":"additional","affiliation":[{"name":"Center for Research and Training in Skin Diseases and Leprosy Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Shokri","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, School of Medicine, Sina Hospital Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Nazar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sina Hospital, School of Medicine Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2024.101821"},{"issue":"8","key":"e_1_2_15_3_1","article-title":"Methotrexate Toxicity\u2010Induced Pancytopenia and Mucocutaneous Ulcerations in Psoriasis","volume":"16","author":"Surapaneni D.","year":"2024","journal-title":"Cureus"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/7693602"},{"issue":"12","key":"e_1_2_15_5_1","article-title":"Low\u2010Dose Methotrexate Toxicity Presenting as Pancytopenia","volume":"14","author":"Dhillon G. 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