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.