Anne-Marie Bégin1, Marie-Lawrence Monfette1, Étienne Boudrias-Dalle2, Emmie Lavallée3, Vanessa Samouelian4,5, Denis Soulières4,6, Miguel Chagnon7, Marie-Andrée Fournier1,4, Nathalie Letarte1,4,8, Jean-Philippe Adam9,10. 1. Department of Pharmacy, Centre hospitalier de l'Université de Montréal, Montreal, Canada. 2. Department of Pharmacy, CIUSSS du Centre-Sud-de-l'Île-de-Montréal, Montréal, Canada. 3. Department of Pharmacy, CISSS de Lanaudière, Joliette, Canada. 4. Centre de recherche du CHUM, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada. 5. Division of Gynecologic Oncology, Centre hospitalier de l'Université de Montréal, Montréal, Canada. 6. Division of Hematology-Oncology, Centre hospitalier de l'Université de Montréal, Montréal, Canada. 7. Department of Mathematics and Statistics, Université de Montréal, Montréal, Canada. 8. Faculty of Pharmacy, Université de Montréal, Montréal, Canada. 9. Department of Pharmacy, Centre hospitalier de l'Université de Montréal, Montreal, Canada. jean-philippe.adam.chum@ssss.gouv.qc.ca. 10. Centre de recherche du CHUM, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada. jean-philippe.adam.chum@ssss.gouv.qc.ca.
Abstract
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/m2. 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/m2 and should probably be reinstated in this setting.
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 cancerpatients 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 cancerspatients 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/m2. 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/m2 and should probably be reinstated in this setting.