Pathophysiology, Diagnosis and Clinical Management of Hepatorenal Syndrome: From Classic to New Drugs

Advanced cirrhosis is frequently associated with renal dysfunction. Hepatorenal syndrome (HRS) is characterized by the occurrence of kidney injury in cirrhotic patients in the absence of other identifiable causes. HRS is classified in 2 different types. Type 1 is characterized by acute renal failure and rapid functional deterioration of other organs, usually related to a precipitating event. Type 2 is characterized by slowly progressive renal failure and refractory ascites. Advanced liver disease induces the progression of hemodynamic alterations such as arterial vasodilation of splanchnic circulation and impairment of cardiac function. The resulting ineffective circulating blood volume promotes the activation of both the renin-angiotensin-aldosterone and sympathetic nervous system, by an increase of antidiuretic hormone activity, in an attempt to restore volemia. Despite fluid retention, ascites and dilutional hyponatremia, renal function is often initially preserved by renal production of vasodilators. However, further insults can lead to an imbalance between systemic vasoconstriction and local renal vasodilation, resulting in progressive renal failure. Over the last decade, clinical strategies to prevent HRS have been improved by a better understanding of the natural history of renal failure in cirrhosis, resulting in a reduction of HRS prevalence in cirrhotic patients. Vasoconstrictor drugs may improve renal function, but the effect on mortality has not yet been established. Vaptans, nonpeptide vasopressin receptor antagonists, may also reduce hyponatraemia and ascites, even if the clinical effects in HRS remain unknown. This review updates the pathophysiology, diagnosis and management of HRS.