Hepatorenal syndrome: pathogenesis and novel pharmacological targets

Hepatorenal syndrome is functional, reversible renal failure that occurs in patients with advanced liver cirrhosis or acute hepatic failure. The fundamental problem in hepatorenal syndrome is renal ischemia secondary to hypotension and profound renal cortical vasoconstriction. Sinusoidal hypertension and its associated splanchnic arterial vasodilatation initiate a cascade of events leading to activation of systemic and local vasoconstrictors and depletion of local renal vasodilators. Therapy with vasopressin V(1) receptor and alpha-adrenergic agonists, and plasma expanders, reverses type I and type II hepatorenal syndrome and improves survival. Large randomized, controlled, multicenter trials are needed to determine which drug is most effective, as well as the optimal dose and duration of treatment.