Effect of mannitol on acute kidney injury induced by cisplatin

Purpose Acute kidney injury (AKI) is a frequent dose-limiting toxicity induced by cisplatin. Mannitol has been used in hydration protocols to mitigate this adverse event but its role remains controversial. The aim of this study is to define the impact of mannitol on AKI in patients receiving cisplatin. Methods This retrospective observational study was conducted in cancer patients who received at least one dose of cisplatin between September 2010 and December 2016 at the Centre hospitalier de l’Université de Montréal. The primary outcome of this study was the comparison of all grade cisplatin-associated AKI between hydration protocols with or without mannitol. Results A total of 1821 patients were included of which 658 received mannitol whilst 1163 received hydration alone. The risk of all grade cisplatin-associated AKI was significantly lower for the mannitol group (Hazard Ratio (HR) = 0.62; 95% CI [0.42, 0.89]). This result was mainly driven by gynecologic (HR = 0.50), upper gastrointestinal (HR = 0.32), urinary tract malignancies (HR = 0.29) and lymphoma (HR = 0.33). No significant difference was seen for head and neck (HN), lung, germ cells and other cancers. However, HN cancers patients receiving mannitol had fewer grade 2 and 3 AKI. Significantly fewer AKI events were observed in HN, lung, upper gastrointestinal and urinary tract cancer when mannitol was added for cisplatin dose <75 mg/m 2 . Conclusion Although the results were generally driven by a decrease of grade 1 AKI for most cancers, the greatest benefit of mannitol was seen with cisplatin doses lower than 75 mg/m 2 and should probably be reinstated in this setting.