A nephrology perspective on the clinical impact and management of delayed high-dose methotrexate elimination

INTRODUCTION: Delayed methotrexate elimination (DME) is observed in ~15% of treatment cycles in patients with cancer receiving high-dose methotrexate (HDMTX). Given the strong association between DME and nephrotoxicity, oncologists might benefit from the input of a nephrologist/medical oncologist with a focus on nephrology when assessing and planning treatment for patients requiring HDMTX. AREAS COVERED: Identifying patients who are at risk of DME and related acute kidney injury (AKI), and developing a bespoke assessment and monitoring plan (with a focus on kidney assessment and monitoring), may help to reduce the risk of complications and enable the continuation of HDMTX treatment, hopefully optimizing long-term survival outcomes. EXPERT OPINION: In this perspective article, based on a search of PubMed literature and expert opinion, we explore the definition and causes of DME and AKI, and the impact of these on patients receiving HDMTX, and examine the key risk factors and early indicators of DME and AKI. A pathway with a nephrology focus is suggested for the assessment, monitoring, and treatment of patients with or at risk of DME.