Oxaliplatin-associated nephrotoxicity: clinical patterns, renal pharmacokinetics, and mechanistic insights.

Abstract

Purpose of review: OXA, a third-generation platinum-based chemotherapeutic agent widely used in gastrointestinal malignancies, is generally regarded as less nephrotoxic than earlier platinum compounds such as cisplatin. However, growing clinical reports and mechanistic studies indicate that renal injury can occur in a subset of patients and may be underrecognized. This review aims to synthesize current evidence on OXA-associated renal dysfunction by integrating clinical patterns of injury with pharmacokinetic behavior and mechanistic pathways relevant to kidney toxicity.

Methods: A focused literature search was conducted in PubMed, Google Scholar, and ScienceDirect for studies published up to December 10, 2025, using keywords related to OXA and renal injury. Additional relevant publications were identified through citation tracking using ResearchRabbit. Records were screened and managed using Rayyan, with duplicate removal performed prior to eligibility assessment. Clinical reports, observational studies, and experimental investigations evaluating renal outcomes following OXA exposure were included, while non-original articles, non-English publications, studies lacking renal assessment, and reports with major confounding nephrotoxic therapies were excluded.

Results: Evidence indicates that OXA-associated nephrotoxicity, although less frequent than cisplatin-induced injury, is clinically relevant. Reported manifestations include AKI, acute tubular necrosis, proximal tubular dysfunction, immune-mediated hemolysis with pigment nephropathy, and tubulointerstitial nephritis. Mechanistic studies implicate transporter-mediated renal handling, oxidative stress, inflammatory signaling, DNA damage responses, and segment-specific tubular vulnerability. Pharmacokinetic factors, cumulative exposure, combination regimens, and pre-existing renal impairment further influence susceptibility.

Conclusion: OXA cannot be considered entirely free from renal adverse effects. Improved clinical vigilance, mechanistic insight, and risk-adapted monitoring strategies are essential to optimize patient safety while maintaining therapeutic efficacy.