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Abstract
Acute kidney injury (AKI) is among the most frequent and consequential organ toxicities of cancer chemotherapy, contributing to dose reduction, treatment discontinuation, chronic kidney disease, and mortality. Chemotherapy-induced AKI is, in most cases, not idiosyncratic: it reflects a mechanistically defined pharmacological injury determined by the interaction between a nephrotoxic agent and specific renal transport, metabolic, and vascular pathways. Cisplatin enters proximal tubular cells through organic cation transporter 2 (OCT2) and copper transporter 1 (CTR1), triggering mitochondrial dysfunction and apoptosis; ifosfamide generates the tubular toxin chloroacetaldehyde, producing Fanconi syndrome; high-dose methotrexate precipitates within the acidic tubular lumen; antiangiogenic agents disrupt podocyte-endothelial vascular endothelial growth factor (VEGF) signaling, producing proteinuria, hypertension, and thrombotic microangiopathy; and immune checkpoint inhibitors provoke acute interstitial nephritis. However, mechanistic intelligibility should not be conflated with clinical preventability. For several agents — most notably ifosfamide tubulopathy and checkpoint inhibitor nephritis — no effective prophylaxis exists, and even for cisplatin, AKI occurs in approximately a quarter to a third of patients despite optimal hydration. This review therefore advances a deliberately calibrated thesis: mechanistic understanding reliably guides monitoring and mitigation, and identifies rational renoprotective targets, but does not yet render chemotherapy-induced AKI reliably preventable across agents. We critically evaluate the evidence for established renoprotective strategies, the real-world limitations of emerging biomarkers and rescue therapies including glucarpidase, the diagnostic pitfalls of creatinine-based AKI definition in sarcopenic cancer patients, and the underappreciated transition from AKI to chronic kidney disease in cancer survivors. A four-domain framework for nephrotoxicity risk stratification is proposed, with explicit attention to where current evidence is strong and where it remains aspirational.
Keywords: acute kidney injury; chemotherapy nephrotoxicity; cisplatin; organic cation transporter 2; thrombotic microangiopathy; tumor lysis syndrome; chronic kidney disease; renoprotection
Authors: Khalid Omer Alfarouk, Amel A. Mohamed
Affiliation: Zamzam University College, Khartoum, Sudan; King Salman Armed Forces Hospital, Tabuk, Saudi Arabia
Vol. 1, Issue 1 · June 2026 · pp. 22–28