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Lars Bergmann, Hartmuth Sebastian Burkhard Nowak, Winfried Siffert, Jürgen Peters, Michael Adamzik, Björn Koos, Tim Rahmel

• Since the functionally important \(\it AQP5\) -1364A/C single nucleotide promoter polymorphism alters key mechanisms of inflammation and survival in sepsis, it may affect the risk of an acute kidney injury. Accordingly, we tested the hypothesis in septic patients that this \(\it AQP5\) polymorphism is associated with major adverse kidney events and also validated its impact on 90-day survival. In this prospective observational monocentric genetic association study 282 septic patients were included and genotyped for the \(\it AQP5\) –1364A/C polymorphism (rs3759129). The primary endpoint was the development of major adverse kidney events within 30 days. In AC/CC genotypes, major adverse kidney events were less frequent (41.7%) than in AA genotypes (74.3%; OR:0.34; 95%-CI: 0.18–0.62; \(\it p\) < 0.001). Ninety-day survival was also associated with the \(\it AQP5\) polymorphism (\(\it p\) = 0.004), with 94/167 deaths (56.3%) in AA genotypes, but only 46/115 deaths (40.0%) in C-allele carriers. Multiple proportional hazard analysis revealed AC/CC genotypes to be at significantly lower risk for death within 90 days (HR: 0.60; 95%-CI: 0.42-0.86; \(\it p\) = 0.006). These findings confirm the important role of the AQP5 -1364A/C polymorphism as an independent prognostic factor in sepsis. Furthermore, we demonstrate a strong association between this \(\it AQP5\) polymorphism and susceptibility for major adverse kidney events suggesting a promising characteristic in terms of precision medicine.