Publication:

Renal function and hydration strategies in high-dose methotrexate chemotherapy: a systematic review (2015-2025)

High-dose methotrexate (HDMTX) remains a cornerstone in the treatment of osteosarcoma, lymphoma, and acute lymphoblastic leukemia. Its therapeutic efficacy is tempered by nephrotoxicity risks, necessitating rigorous renal function screening, hydration protocols, and timely rescue strategies. This systematic review synthesized evidence published between 2015 and 2025 on renal thresholds, fluid management, and adjunctive interventions to optimize HDMTX safety and efficacy. Databases searched included PubMed, Embase, Cochrane Library, and Scopus. Inclusion criteria encompassed clinical trials, cohort studies, and guidelines addressing renal function, hydration, and rescue in HDMTX.  Eleven eligible studies were reviewed. Findings highlight the importance of glomerular filtration rate (GFR) ≥ 60 ml/min/1.73m² as a prerequisite for HDMTX. Pre-infusion hydration (≥2.5 l/m²/day) and urinary alkalinization (pH > 7.0) are consistently recommended to prevent methotrexate crystallization.  Leucovorin rescue timing and dosing are guided by serum MTX levels, while glucarpidase is reserved for delayed clearance or acute kidney injury (AKI). This review reinforces the need for standardized renal screening and hydration protocols, especially in older adults and those with borderline renal function. Early identification of delayed clearance and access to rescue agents are critical to reducing toxicity and improving outcomes.