Albumin: New Roles beyond Volume Expander

Albumin is a 65-70kDa protein that accounts for approximately half the total plasma protein content in humans. For many years,it was thought that its only two functions were to bind to various substances so they could be transported or stabilized, andto provide a major part of the plasma oncotic pressure, also called colloid osmotic pressure.Research over the past 3 decades has established numerous other essential roles of albumin. Moreover, it has been found toimprove outcomes not just in liver disease but a number of other pathologic conditions including stroke, sepsis, acute lung injuryand subarachnoid hemorrhage. In liver disease, albumin has been found to be useful to help treat or manage spontaneous bacterialperitonitis, hepatorenal syndrome, resistant ascites, post-paracentesis circulatory dysfunction and hyponatremia.The other mechanisms of action besides its colloid osmotic effect can be grouped into several categories. These include substancedetoxification/stabilization, metal binding, cell stabilization and immune/anti-inflammatory effects. At the cellular level, it mediatesmany of these effects due to its small size, binding domains, charge and ability to enter a variety of cells. It thus subservesseveral important physiological functions in health, but in cirrhosis, several of these functions have been demonstrated to beimpaired.Specific examples of these normal beneficial cellular effects include reduction of oxidative stress and immune stabilizing. Albuminenters endothelial cells and in animal models of liver disease, has been shown to reduce the deleterious effects of LPS and endotoxinprimarily through a TLR-mediated effect. It also improves endothelial function as judged by markers such as Von WillebrandFactor production. It can also improve neutrophil function to reduce infection risk in cirrhosis. In the kidney, it appears to restorerenal blood flow autoregulation by an unclear mechanism. but one that seems to be largely independent of its effect as a volumeexpander. Several studies have demonstrated reduction of oxidative stress in the liver and vasculature by albumin.The function of numerous other organ systems in cirrhosis is known to be altered, and dysfunctional albumin may play rolesin those systems’ dysfunction.The role of albumin in the blood vessels and vasculature has been studied but possible effects in the cirrhotic lung and hearthave not yet been clarified. These areas are fertile ground for future research.