Risk factors for acute kidney injury after high-dose methotrexate therapy: a single-center study and narrative review

To assess the risk factors associated with high-dose methotrexate (HDMTX) (≥ 1 g/m²) treatment-induced acute kidney injury (AKI).

Patients who received HDMTX from July 2014 to August 2019 in one medical center were enrolled. The patients' demographic, laboratory, and medication data were collected and compared between groups with or without AKI. Risk factors of HDMTX-induced AKI were explored using univariate and multivariate logistic regression analyses. Additionally, we searched and summarized previous studies to identify key correlates of AKI in a narrative review.

We enrolled 59 patients who had received 200 HDMTX courses. The incidence of HDMTX-induced nephrotoxicity was 9.5%. Multivariate logistic regression revealed that male sex (odds ratio [OR], 4.20; P = .037), and angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) (OR, 5.18; P = .016) were significantly associated with AKI. Diuretics with urinary acidification, such as loop diuretics, were also a key factor in AKI (OR, 4.91; P = .018). Furthermore, a forest plot identified 21 predictors from nine additional cohort studies showing correlations with the development of AKI.

Male sex, ACEIs/ARBs, and diuretics with urinary acidification are associated with AKI. Furthermore, laboratory data should be monitored to assess AKI risk before HDMTX therapy, especially in elderly patients with obesity, diabetes, or acute lymphoblastic leukemia.