title: Outcomes Associated with Reducing the Urine Alkalinization Threshold in Patients Receiving High-Dose Methotrexate.
abstract: OBJECTIVE
  Urine alkalinization increases methotrexate (MTX) solubility and reduces the risk of nephrotoxicity. The objectives of this study were to determine whether a reduction in the urine pH threshold from 8 to 7 in patients receiving high-dose methotrexate (HDMTX) results in a shorter length of hospital stay, delayed MTX clearance, or higher rates of nephrotoxicity; and to determine whether specific factors were associated with prolonged MTX clearance.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Hematology service of a large university-affiliated teaching hospital in Ottawa, Canada.
  
  
  METHODS
  Sixty-five adults with 150 HDMTX exposures who had elective admissions for HDMTX between September 1, 2014, and December 18, 2015, were included. Thirty-four patients (with 79 HDMTX exposures) had their urine alkalinized to a pH of 8 or higher, and 31 patients (with 71 HDMTX exposures) had their urine alkalinized to a pH of 7 or higher, after an institutional change in the urine pH threshold from 8 to 7 was implemented on May 1, 2015.
  
  
  RESULTS
  Data related to patient demographics, urine alkalinization, MTX serum concentration monitoring, hospital length of stay, and renal function were collected retrospectively from patients' electronic health records. Lowering the urine pH threshold from 8 to 7 did not significantly affect hospital length of stay (absolute difference 3.5 hrs, 95% confidence interval -4.0 to 10.9) or clearance of MTX (elimination rate constant 0.058 in the pH of 7 or higher group vs 0.064 in the pH of 8 or higher group, p=0.233). Nephrotoxicity rates were similar between groups (15.5% in the pH of 7 or higher group vs 10.1% in the pH of 8 or higher group, p=0.34). Higher MTX dose and interacting medications (e.g., proton pump inhibitors and sulfonamide antibiotics) were significantly associated with delayed MTX elimination.
  
  
  CONCLUSIONS
  No significant differences in HDMTX-associated hospital length of stay, MTX clearance, or rates of nephrotoxicity were noted between patients in the urine pH of 7 or higher and 8 or higher groups. Interacting medications and higher MTX dose were associated with delayed MTX elimination, suggesting that a closer review of interacting medications before HDMTX administration may be warranted.
authors.affiliation: Pharmacy Department, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Drost
authors.affiliation: Pharmacy Department, The Ottawa Hospital, Ottawa, Ontario, Canada.|The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Wentzell
authors.affiliation: Pharmacy Department, The Ottawa Hospital, Ottawa, Ontario, Canada.|The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Giguère
authors.affiliation: Pharmacy Department, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Darcy L
authors.initials: DL
authors.lastname: McLurg
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Sabloff
authors.affiliation: Pharmacy Department, The Ottawa Hospital, Ottawa, Ontario, Canada.|The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Salmaan
authors.initials: S
authors.lastname: Kanji
authors.affiliation: Pharmacy Department, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Tiffany T
authors.initials: TT
authors.lastname: Nguyen
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000517:prevention & control / Q000652:urine*; D000328:Adult; D000368:Aged; D000863:Antacids / Q000494:pharmacology / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000652:urine; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007902:Length of Stay / Q000639:trends; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D008727:Methotrexate / Q000009:adverse effects* / Q000652:urine*; D008875:Middle Aged; D012189:Retrospective Studies; D017693:Sodium Bicarbonate / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014556:Urine / Q000469:parasitology / Q000502:physiology
chemical_list: D000863:Antacids; D000964:Antimetabolites, Antineoplastic; D017693:Sodium Bicarbonate; D008727:Methotrexate
keywords: adverse drug reactions; drug safety; hematology; pharmacokinetics