Articulo

In-Depth Review

Hepatorenal Syndrome: Pathophysiology and Management
Hani M. Wadei,*† Martin L. Mai,*† Nasimul Ahsan,*† and Thomas A. Gonwa*†
Departments of *Transplantation and †Medicine, Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Jacksonville, Florida
Clin J Am Soc Nephrol 1: 1066 –1079, 2006. doi: 10.2215/CJN.01340406

n the late 19th century, reports byFrerichs (1861) and Flint (1863) noted an association among advanced liver disease, ascites, and oliguric renal failure in the absence of significant renal histologic changes (1). Almost 100 yr later, in a seminal article by Hecker and Sherlock (2), the pathogenesis of hepatorenal syndrome (HRS) was unraveled. The authors demonstrated the lack of major renal histologic changes despite theseverity of kidney failure, linked the deterioration in renal function to impairment of the systemic circulation, and concluded that the underlying mechanism of kidney failure is peripheral arterial vasodilation. On the basis of this hypothesis, their patients were treated with norepinephrine with dramatic but short-lived improvement in urine volume and without a significant change in serum creatinineor urea concentrations. The functional nature of HRS was confirmed further by the ability to transplant kidneys from patients with HRS and the normalization of renal function after liver transplantation (3,4). Subsequent studies by Epstein et al. (5) demonstrated without doubt that splanchnic and systemic vasodilation together with intense renal vasoconstriction is the pathophysiologic hallmarkof HRS. However, despite improved understanding, the prognosis of HRS remained poor, and in the 1970s, the term “terminal functional renal failure” was synonymous with HRS (6). During the last 2 decades, knowledge of the pathogenesis and management of HRS has improved greatly. The present article provides an update on these recent developments.

I

failure with a serum creatinine of 1.5 mg/dl.In type 1 HRS, a precipitating factor frequently is identified, whereas type 2 HRS arises spontaneously and is the main underlying mechanism of refractory ascites.

Pathophysiology
HRS is the most advanced stage of the various pathophysiologic derangements that take place in patients with cirrhosis. The hallmark of HRS is intense renal vasoconstriction that starts at an early time point andprogresses with worsening of the liver disease (7). The underlying mechanisms that are involved in HRS are incompletely understood but may include both increased vasoconstrictor and decreased vasodilator factors acting on the renal circulation. Type 2 HRS is gradually progressive and arises in association with the progression of cirrhosis, whereas type 1 is an acute deterioration in kidneyfunction associated with severe renal vasoconstriction and failure of compensatory mechanisms that are responsible for maintenance of renal perfusion (8). Four interrelated pathways have been implicated in the pathophysiology of HRS. The possible impact of each one of these pathways on renal vasoconstriction and the development of HRS varies from one patient to the other. These pathways include: 1.Peripheral arterial vasodilation with hyperdynamic circulation and subsequent renal vasoconstriction; 2. Stimulation of the renal sympathetic nervous system (SNS); 3. Cardiac dysfunction contributing to the circulatory derangements and renal hypoperfusion; 4. Action of different cytokines and vasoactive mediators on the renal circulation and other vascular beds.

Definition
HRS is a reversiblefunctional renal impairment that occurs in patients with advanced liver cirrhosis or those with fulminant hepatic failure. It is characterized by marked reduction in GFR and renal plasma flow (RPF) in the absence of other cause of renal failure. The hallmark of HRS is intense renal vasoconstriction with predominant peripheral arterial vasodilation. Tubular function is preserved with the absence of...