title: Methotrexate Associated Renal Impairment Is Related to Delayed Elimination of High-Dose Methotrexate.
abstract: Although Methotrexate (MTX) is an effective drug for the treatment of acute lymphoblastic leukemia (ALL), the toxicity remains a significant problem. In this prospective study, fifty-four patients with ALL were enrolled. 3 g or 5 g MTX/m(2) was administered over 24 hours. Serum MTX concentrations were determined in 24, 48, and 96 hours after MTX infusion. Serum creatinine concentrations and creatinine clearance rate (CCR) were determined before and 24 and 48 hours after MTX infusion. A total of 173 courses of MTX infusion were administered. The serum creatinine concentrations did not change much after MTX infusion while the CCR was gradually decreased. MTX clearance status was independently related to CCR decrease, with the risk of 8.07 to develop renal impairment in patients with delayed MTX elimination. Serum creatinine concentration, serum creatinine ratio, CCR, and CCR ratio at 24 hours were all related to MTX elimination delay. Patients with serum creatinine level >35.0 μmol/L, creatinine ratio >1.129, or CCR <100.0 mL/min were more likely to undergo MTX elimination delay. In conclusion, MTX could induce transient renal impairment and compromised renal function will delay MTX clearance. The serum creatinine concentration and the ratio and CCR are useful tools for evaluating MTX elimination status.
authors.affiliation: Division of Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Shi-Long
authors.initials: SL
authors.lastname: Yang
authors.affiliation: Division of Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Fen-Ying
authors.initials: FY
authors.lastname: Zhao
authors.affiliation: Division of Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Song
authors.affiliation: Division of Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Di-Ying
authors.initials: DY
authors.lastname: Shen
authors.affiliation: Division of Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood; D011237:Predictive Value of Tests; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D003404:Creatinine; D008727:Methotrexate