Mannitol versus furosemide for prevention of cisplatin-induced nephrotoxicity in a multicenter retrospective cohort study

Cisplatin (cis-diamminedichloroplatinum [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 patients with cancer 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 the Common Terminology Criteria for Adverse Events (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). Hypertension, cisplatin dose ≥ 75 mg/m², absence of magnesium supplementation, and mannitol use were associated with a higher risk of nephrotoxicity. Stratified analysis demonstrated furosemide's superior nephroprotective effects regardless of nonsteroidal anti-inflammatory drug use. Thus, furosemide was associated with superior renoprotective effects compared with mannitol in CDDP-based chemotherapy regimens, thereby making it a viable therapeutic alternative to mannitol. Large randomized controlled trials are warranted to further validate our findings.