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Abstract Background This study evaluates the association of diuresis and hydration through a new monitoring indicator called $${U}_{sen}$$ U sen and the risk of acute kidney injury in patients treated with cisplatin based-EXTREME regimen. Methods We retrospectively reviewed all the cycles of patients with recurrent and/or metastatic head and neck cancer who received cisplatin based-EXTREME regimen from June 2008 to July 2022. Hydration regimen, urine output and concomitant treatments data were collected on the day of cisplatin infusion and the following day of each course received. Results Of the 110 courses received by 46 patients, 38 (34.5%) results in AKI. No patient characteristics showed a significant difference between AKI (70%) and non-AKI (30%) group. In univariate analysis, dose reduction of cisplatin (odds ratio = 0.166 [0.04; 0.75], p = 0.01)) and $${U}_{sen}$$ U sen >8 (odds ratio = 0.316 [0.133; 0.755], p = 0.015) and cardiac treatments (odds ratio = 3.24 [1.26; 8.52], p = 0.02) were significantly associated with AKI risk. In multivariate analysis, cisplatin dose reduction (odds ratio = 0.129 [0.0241; 0.687], p = 0.016) and $${U}_{sen}$$ U sen >8 (odds ratio = 0.184 [0.0648; 0.523], p = 0.0015) were associated with a risk reduction of cisplatin-related AKI. Concomitant administration of cardiac treatments (odds ratio = 3.18 [1.1; 9.22], p = 0.033) showed an increased risk of cisplatin-related AKI. Conclusion The combination of diuresis and i.v. hydration through the $${U}_{sen}$$ U sen composite score was shown to be associated with cisplatin-induced AKI risk in patients treated with cisplatin based EXTREME regimen. It could be used as a practical indicator to trigger specific clinical management to limit the risk of cisplatin induced AKI.