Sphingosine-1-phosphate receptor signaling during acute kidney injury: The tissue is the issue

Sphingosine-1-phospate is a lipid mediator that has been implicated in protection from acute kidney injury (AKI) by activation of the sphingosine-1-phosphate receptor S1P1R. A recent study demonstrates that mice with induced deletion of S1P1R on endothelial cells experience increased ischemia-induced AKI. These findings have important translational implications. Indeed, S1P1R agonists have been used for the treatment of patients suffering from autoimmune encephalitis. As such, endothelial S1P1R-signaling could be targeted for AKI prevention in surgical patients. Keywords Sphingosine; sphingosine-1-phosphate; adenosine; ischemia; acute kidney injury Acute kidney injury (AKI) is defined by a rapid loss in kidney function – a disease process that contributes significantly to morbidity and mortality of hospitalized patients1. One of the leading causes of AKI is renal ischemia, such as occurs in patients undergoing major surgery. Particularly, patients undergoing cardiac surgery, thoracic surgery and aortic surgery involving cross-clamping of the aorta are very prone to developing AKI in their perioperative course. The search for novel pharmacologic approaches for AKI treatment o