Sphingosine‐1‐phosphate reduces hepatic ischaemia/reperfusion‐induced acute kidney injury through attenuation of endothelial injury in mice

Abstract

Hepatic ischaemia/reperfusion injury (IRI) frequently complicates acute kidney injury (AKI) during the perioperative period. This study was to determine whether hepatic IRI causes AKI and the effect of the sphingosine-1-phosphate (S1P) on AKI. S1P and vehicle were given to mice before ischaemia and mice were subjected to hepatic IRI. Plasma creatinine (PCr), alanine transaminase (ALT), urinary neutrophil gelatinase-associated lipocalin (NGAL) and renal histological changes were determined. As a marker of endothelial injury, vascular permeability was measured. The effect of VPC 23019, a S1P(1) receptor antagonist, was also assessed. Hepatic IRI resulted in liver injury (increased ALT) and systemic inflammation. Kidneys showed elevated inflammatory cytokines, leucocyte infiltration, increased vascular permeability, tubular cell apoptosis and increased urinary NGAL, although PCr did not increase. Pretreatment with S1P resulted in an attenuation of systemic inflammation and kidney injury without any effect on plasma ALT or peripheral lymphocytes. The protective effect of S1P was partially reversed by VPC 23019, suggesting the important contribution of the S1P/S1P(1) pathway to protect against hepatic IRI-induced AKI. The study data demonstrate the important contribution of systemic inflammation and endothelial injury to AKI following hepatic IRI. Modulation of the S1P/S1P(1) receptor pathway might have some therapeutic potential in hepatic IRI-induced kidney injury.