Kidney-Lung-Axis

Acute kidney injury (AKI) is common and develops in 2-5% of hospitalized patients, in 30-60% of intensive care unit (ICU) patients, and 20% of patients within 6 months after kidney transplantation. AKI alone has a 15-30% mortality, but when it occurs in the setting of multiorgan failure, in particular with acute respiratory distress syndrome (ARDS), mortality rises to 60-80%.

Our studies are based on our analysis of lung dysfunction after acute kidney injury and the discovery that kidney injury-released circulating osteopontin induces remote lung inflammation. This involves the induction of lung endothelial leakage, deposition of circulating osteopontin into the lung, and the attraction of myeloid cells (neutrophils and monocyte-derived interstitial macrophages) into the lung, resulting in respiratory failure. (Khamissi et al. Science Advances 2022).

Our results provide mechanistic understanding of the detrimental effects of acute kidney injury on the lung in multiorgan failure and highlight the importance of circulating interorgan crosstalk mediators in the development of complex diseases and secondary organ complications.

We are currently studying how osteopontin induces this kidney-lung phenotype.