Lung‐kidney interactions during pneumonia and acute kidney injury

Abstract

Sepsis is a major contributor to organ failure in critically‐ill patients. Mortality drastically increases with the number of failing organs. Both lung and kidney injury are very common in severe sepsis. The aim of this study was to investigate kidney‐lung interactions during pneumonia‐induced sepsis and acute kidney injury (AKI).We have sequentially combined murine models of folic‐acid (FA)‐induced AKI and P. aeruginosa‐induced pneumonia (PNA). A subgroup of mice received a neutrophil (PMN)‐depleting antibody or respective control before induction of PNA. 24h after induction of PNA, we measured oxygen saturation (SpO2), plasma creatinine (pCrea), and P. aeruginosa colony‐forming units (CFUs) in lung homogenates. Statistical analysis included one‐way ANOVA, Kruskal‐Wallis one‐way analysis of variance, post‐hoc Student‐Newman‐Keuls test, and t‐test. All data is given as median (inter‐quartile range).PNA leads to severe AKI in mice, which seems to be independent of PMNs. In a PMN‐dependent model of PNA, AKI worsens PNA. As AKI is known to impair pulmonary recruitment of PMNs [1], one can hypothesize that the effects of AKI on pneumonia are mediated by PMNs. In summary, we show functionally relevant kidney‐lung interactions during PNA and AKI, which are partially PMN‐dependent.