Risk factors for high-dose methotrexate associated acute kidney injury in patients with hematological malignancies.

High dose methotrexate (HDMTX)-induced acute kidney injury (AKI) is a well-known adverse event in hemato-oncology patients. Our purpose was to define factors and setup cut offs that may help better identify patients at-risk for developing AKI following HDMTX. All consecutive patients who received MTX dose ≥1 g were retrospectively reviewed. We compared patients with or without renal toxicity. We used a logistic regression model to define baseline variables associated with AKI. Overall survival (OS) was estimated by the Kaplan-Meier method employing log-rank test. Between 2012-2017, 160 patients were included with a total of 265 courses. Indications included: primary central nervous lymphoma (CNS) lymphoma, CNS prophylaxis in other lymphoma types, acute lymphatic leukemia and others. Median age at diagnosis was 58 years (range, 18-84), 54% were males, median MTX dose was 1941 mg/m2 (range, 743-5442) and AKI developed in 9% of drug administrations (n = 24). In univariate analysis: age > 40, LDH > 380 u/L, eGFR <112 mL/min, albumin <3.6 mg/dL at baseline and Charlson comorbidity index were associated with AKI. In multivariable analysis, only LDH > 380 units/L (OR = 4.1, 95%CI 1.04-20.9, P = 0.04) and albumin levels <3.6 g/dL (OR = 4.17, 95%CI 1.04-6.5, P = 0.04) remained significant. In patients with AKI, median drug elimination was longer (eight days vs 5 days). In 80% of cases, the creatinine levels returned to normal within 1 month. Yet, the median survival of patients who developed AKI was 37 months, compared to 145 months in patients without AKI (Log rank = 0.015). In conclusion, LDH > 380 units/L and albumin <3.6 g/dL were the strongest factors associated with AKI in patients receiving HDMTX. Although the rise in creatinine levels was almost uniformly reversible, AKI was associated with increased mortality rates. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.