The use of terlipressin in hepatorenal syndrome

Hepatorenal syndrome (HRS) is a potentially reversible cause of acute renal failure that occurs in patients with hepatic failure resulting from advanced cirrhosis. It is characterized by impaired kidney function in the setting of normal renal parenchyma, alterations in cardiovascular function, splanchnic vasodilation, and overactivity of the sympathetic nervous and the renin-angiotensin systems causing severe arterial vasoconstriction. Clinically, patients will present with the classic signs and symptoms of liver and renal failure, such as ascites, jaundice, coagulopathy, hepatic encephalopathy, and decreased urine output. Patients with cirrhosis are thought to have extreme circulatory dysfunction caused by portal hypertension-induced release of vasodilators (primarily nitric oxide) into the splanchnic circulation, causing local vasodilation. Terlipressin is a synthetic long-acting analogue of vasopressin in which lysine is substituted for arginine at position 8 and the N-triglycyl residue. It has been shown to cause direct vasoconstriction of the systemic arteriolar and splanchnic vasculature. It affects the V1 vasopressin receptors of systemic vasculature more strongly than the V2 vasopressin receptors of the kidneys. Although it is not currently approved by the U.S. Food and Drug Administration, it has been widely studied and is currently being used in other countries for the treatment of HRS. Terlipressin is quickly emerging as a promising treatment of hepatorenal syndrome. Today its best use may be in improving renal function in preparation for liver transplantation, which has shown to reduce post-transplant morbidity and mortality.