Cisplatin-induced renal toxicity: an integrated view of molecular pathways and emerging therapeutic targets—a comprehensive review

Cisplatin is a widely used chemotherapeutic agent effective against a variety of solid tumors; however, its clinical utility is limited by dose-dependent nephrotoxicity. Cisplatin-induced renal injury involves a complex pathophysiology, including transporter-mediated uptake, biotransformation into reactive metabolites, oxidative stress, mitochondrial dysfunction, DNA damage, inflammation, and activation of cell death pathways such as apoptosis, necroptosis, and ferroptosis. Hydration therapy remains the primary clinical intervention; however, it provides limited protection, particularly in high-risk patient populations. Emerging biomarkers such as NGAL, KIM-1, cystatin C, and IL-18 enable earlier and more accurate detection of renal injury, whereas conventional markers, including serum creatinine and blood urea nitrogen (BUN), lack sensitivity for early diagnosis. Several pharmacological strategies targeting oxidative stress, inflammasome activation, mitochondrial dysfunction, and regulated cell death pathways are being investigated for their nephroprotective potential. Compounds such as MitoQ, ferrostatin-1, necrostatin-1, and NLRP3 inhibitors have demonstrated promising effects in preclinical models by attenuating cisplatin-induced renal damage. In addition, emerging approaches, including growth factors, stem cell-derived exosomes, and biomarker-guided therapeutic strategies, offer promising avenues for clinical translation. Overall, this review highlights the need for individualized, multi-targeted strategies to prevent and manage cisplatin-induced nephrotoxicity by integrating mechanistic insights, clinical challenges, and emerging therapeutic advances. Such approaches may improve cancer treatment outcomes while preserving renal function.