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Tim Rahmel, Hartmuth Sebastian Burkhard Nowak, Katharina Rump, Winfried Siffert, Jürgen Peters, Michael Adamzik

• \(\bf Background\) Aquaporin 5 (\(\it AQP5\)) expression impacts on cellular water transport, renal function but also on key mechanisms of inflammation and immune cell migration that prevail in sepsis and ARDS. Thus, the functionally relevant \(\it AQP5\) -1364A/C promoter single nucleotide polymorphism could impact on the development and resolution of acute kidney injury (AKI). Accordingly, we tested the hypothesis that the \(\it AQP5\) promoter -1364A/C polymorphism is associated with AKI in patients suffering from pneumonia evoked ARDS. \(\bf Methods\) This prospective study included 136 adult patients of Caucasian ethnicity with bacterially evoked pneumonia resulting in ARDS. Blood sampling was performed within 24 hours of ICU admission and patients were genotyped for the \(\it AQP5\) promoter -1364A/C single nucleotide polymorphism. The development of an AKI and the cumulative net fluid balance was described over a 30-day observation period and compared between the AA and AC/CC genotypes, and between survivors and non-survivors. \(\bf Results\) Incidence of an AKI upon admission did not differ in AA (58%) and AC/CC genotype carriers (60%; p = 0.791). However, on day 30, homozygous AA genotypes (57%) showed an increased prevalence of AKI compared to AC/CC genotypes (24%; p = 0.001). Furthermore, the AA genotype proved to be a strong, independent risk factor for predicting AKI persistence (odds-ratio: 3.35; 95%-CI: 1.2–9.0; p = 0.017). While a negative cumulative fluid balance was associated with increased survival (p = 0.001) the \(\it AQP5\) promoter polymorphism had no impact on net fluid balance (p = 0.96). \(\bf Conclusions\) In pneumonia evoked ARDS, the AA genotype of the \(\it AQP5\) promoter polymorphism is associated with a decreased recovery rate from AKI and this is independent of fluid balance. Consequently, the role of \(\it AQP5\) in influencing AKI likely rests in factors other than fluid balance.