Comparative Efficacy of Mannitol versus Furosemide for Prevention of Cisplatin-Induced Nephrotoxicity: A Retrospective Multicenter Study

Abstract Background: Cisplatin (CDDP) is a widely used anticancer drug with a significant risk of nephrotoxicity. This study aimed to compare the nephroprotective effects of mannitol and furosemide as forced diuretics in patients receiving CDDP-based chemotherapy. This multicenter retrospective study analyzed 472 cancer patients receiving CDDP (≥60 mg/m²) with either mannitol or furosemide as forced diuretics. Patient characteristics were balanced using inverse probability treatment weighting. Nephrotoxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) ver. 5.0 criteria. The results showed that the incidence of nephrotoxicity was significantly lower in the furosemide group than in the mannitol group (6.2% vs. 23.2%, p<0.007). The mean serum creatinine increase was significantly lower with furosemide (21.7±19.3%) than with mannitol (29.5±40.7%, p=0.007). Multivariate analysis identified hypertension, cisplatin dose ≥75 mg/m², absence of magnesium supplementation, and mannitol use as independent risk factors for nephrotoxicity. Stratified analysis demonstrated furosemide's superior nephroprotective effects regardless of nonsteroidal anti-inflammatory drug use. Therefore, our findings suggest that furosemide provides superior nephroprotection compared to mannitol in CDDP-based chemotherapy regimens. Furosemide is a viable therapeutic alternative to mannitol. Large prospective randomized controlled trials are warranted to further validate these findings.