Abstract
Background: High-dose methotrexate (HDMTX) chemotherapy is associated with a significant risk of acute kidney injury (AKI). Acetazolamide is thought to increase methotrexate solubility via urinary alkalinisation, potentially reducing the risk of crystalline nephropathy. A tertiary hospital has included acetazolamide in its HDMTX protocols, although data on the risks and benefits are limited. This study evaluated the role of acetazolamide in managing patients receiving HDMTX and identified risk factors for AKI. Methods: The retrospective cohort pilot study included consecutive hospital patients who received HDMTX (≥500 mg/m(2)). Data collected from digital medical records included demographics, comorbidities, methotrexate dosages and serum concentrations, and pathology results. The development of AKI was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Relationships between variables and AKI were initially assessed using Mann-Whitney U-tests and chi-square tests, and significant variables were further analysed using logistic regression to identify independent predictors of AKI. Results: Among 66 HDMTX treatment cycles in 31 patients, AKI occurred in 0/7 cycles with acetazolamide versus 14/59 cycles without (p = 0.33). Increasing age, the presence of hypertension, and concurrent use of beta-lactam antibiotics were associated with the development of AKI. Age was identified as the strongest independent risk factor for AKI (odds ratio 1.12, p = 0.034). Conclusions: Optimising management protocols, especially for older patients, is essential to reduce AKI risk during HDMTX therapy. While acetazolamide did not appear to reduce the risk of AKI, this pilot study was limited by a small sample size. Large randomised controlled trials are needed to assess efficacy and patient outcomes.