Outcomes Associated with Reducing the Urine Alkalinization Threshold in Patients Receiving High-Dose Methotrexate

Abstract

Study Objectives

Urine alkalinization increases methotrexate 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 methotrexate clearance, or higher rates of nephrotoxicity; and to determine whether specific factors were associated with prolonged methotrexate clearance.

Design

Retrospective cohort study.

Setting

Hematology service of a large, university-affiliated, teaching hospital in Ottawa, Canada.

Patients

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 ≥ 8, and 31 patients (with 71 HDMTX exposures) had their urine alkalinized to a pH ≥ 7, after an institutional change in the urine pH threshold from 8 to 7 was implemented on May 1, 2015.

Measurements and Main Results

Data related to patient demographics, urine alkalinization, methotrexate 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 3.45 hrs, 95% CI –4.03–10.94) or clearance of methotrexate (elimination rate constant 0.058 in the pH ≥ 7 group vs 0.064 in the pH ≥ 8 group, p=0.233). Nephrotoxicity rates were similar between groups (15.5% in the pH ≥ 7 group vs 10.1% in the pH ≥ 8 group, p=0.34). Higher MTX dose and interacting medications (e.g., proton pump inhibitors and sulfonamide antibiotics) were significantly associated with delayed methotrexate elimination.

Conclusion

No significant differences in HDMTX-associated hospital length of stay, methotrexate clearance, or rates of nephrotoxicity were noted between patients in the urine pH ≥ 7 and ≥ 8 groups. Interacting medications and higher MTX dose were associated with delayed methotrexate elimination, suggesting that a closer review of interacting medications prior to HDMTX administration may be warranted.

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