OPTIMIZING RENAL SAFETY IN HIGH -DOSE METHOTREXATE THERAPY: A COMPREHENSIVE REVIEW

Methotrexate (MTX) remains the first-line treatment option even in large doses (HD-MTX) for solid tumors and hematologic malignancies. However, MTX related toxicity to the kidneys has been a major clinical issue even with the use of effective drugs; this has caused among other things increased hospital stays, delays in treatment, and acute kidney injury (AKI) in some cases of allergic reactions. As the kidneys are the main organs that eliminate MTX, the renal function is crucial for the safe use of the drug. • This review integrates the extensive data from the recent clinical trials (2020–2025) and mechanistic studies to provide the most up-to-date knowledge of MTX nephrotoxicity, risk factors, novel biomarkers, and changing treatment paradigms. The review focuses on and emphasizes the significant clinical outcomes of recent studies, discusses treatment techniques such as glucarpidase, hydration schedules, and urine alkalinization, and even evaluates the new methods of AI-backed prediction models and personalized dosing. It is the aim of the review to support practitioners, pharmacists, and cancer doctors in making substantial progress in the prevention, early detection, and best management of MTX-induced renal impairment.