Support Care Cancer. 2025 Nov 20;33(12):1102. doi: 10.1007/s00520-025-10171-y.
ABSTRACT
BACKGROUND: Cisplatin causes nephrotoxicity in approximately 30% of patients. Mannitol has been proposed as a nephroprotective agent, yet the clinical evidence remains inconclusive.
METHODS: We systematically searched PubMed, EMBASE, and the Cochrane Library through December 2024 for randomized controlled trials (RCTs) evaluating mannitol versus control interventions for prevention of cisplatin-induced nephrotoxicity. The primary outcome was acute kidney injury (AKI), standardized across CTCAE, AKIN, and RIFLE systems. Given heterogeneous comparators, analyses were stratified by control type without cross-comparator pooling. Odds ratios (ORs) were used for AKI; risk differences (RDs) were used for adverse events. Pooled estimates were generated only when ≥ 5 trials were available per stratum.
RESULTS: Nine RCTs (357 participants) were included. For severe AKI (grade ≥ 2), three small trials (n = 164) were available. Two placebo-controlled studies showed lower AKI risk with mannitol (absolute reductions ~ 15-20%), while one furosemide-controlled study showed no clear difference. These preliminary observations require confirmation in larger trials. For overall AKI (grade ≥ 1; six trials, n = 297), results were inconsistent across studies. Renal function outcomes were heterogeneous: one placebo-controlled trial favored mannitol, one hydration-controlled trial favored control, and a furosemide-controlled trial showed minimal difference. Adverse events were sparsely reported: no consistent differences were seen for electrolyte or hematological toxicities, while several studies suggested modest reductions in nausea/vomiting and a possible increase in diarrhea.
CONCLUSIONS: Based on only three small trials (n = 164), preliminary trends suggest mannitol might reduce severe AKI in cisplatin-treated patients, particularly versus placebo. However, this evidence is insufficient to support clinical implementation. The observed protective trend should be considered hypothesis-generating rather than definitive. Effects on overall AKI, renal function, and toxicities remain inconclusive. Larger, well-designed RCTs with adequate statistical power are urgently needed before mannitol can be recommended for routine nephroprotection in clinical practice.
PMID:41266849 | DOI:10.1007/s00520-025-10171-y
