578 ALBUMIN INFUSION IMPROVES SYSTEMIC AND RENAL BLOOD FLOW AUTOREGULATION BY RESTORATION OF ENDOTHELIAL DYSFUNCTION

Background and Aims: Hemodynamic alterations in liver failure are associated with endothelial activation (EA), dysfunction (ED), inflammation and activation of vasoconstrictor systems. Albumin is a multifunctional protein which is reduced in quantity and function in liver failure. Albumin infusion in cirrhotic patients is associated with improvements in systemic hemodynamics and renal blood flow autoregulation but the mechanisms are unclear. This study test the hypothesis that albumin modulates these beneficial effects through restoration of endothelial function. Methods: Patients: Subjects with refractory ascites (n = 12) or acuteon-chronic liver failure with acute kidney injury (AKI, n = 10) received albumin 40–60 gr/d (3–4 days). Hemodynamics (cardiac output – CO, mean arterial pressure –MAP, renal blood flow – RBF), oxidative stress (F2a-isoprostanes), EA/ED (von Willebrand factor – vWF, nitrate – NO) and renal function were assessed at baseline and after treatment. In vivo: Analbuminemic and wild-type rats were assessed for markers of ED (ADMA-asymmetric dimethylarginine-), hemodynamics and renal function 6 weeks after sham/bile duct ligation (BDL) surgery. In vitro: Human umbilical vein endothelial cells (HUVECs) were stimulated with lipopolysaccharide (LPS) with or without albumin. We studied markers of EA (E-selectin, VCAM1) and intracellular ROS (reactive oxygen species).