Sindrome Hepatorenal

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

I

n the late 19th century,reports by Frerichs (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 despitethe
severity 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 inserum creatinine or 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 thepathophysiologic hallmark
of 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.

Definition
HRS is areversible functional 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 theabsence of proteinuria or histologic changes in the kidney. Two subtypes of HRS have been
identified: Type 1 HRS is a rapidly progressive renal failure that
is defined by doubling of initial serum creatinine to a level 2.5
mg/dl or by 50% reduction in creatinine clearance to a level
20 ml/min in 2 wk. Type 2 HRS is a moderate, steady renal

Published online ahead of print. Publication dateavailable at www.cjasn.org.
Address correspondence to: Dr. Thomas A. Gonwa, Mayo Clinic and Foundation,
4205 Belfort Road, Suite 1100, Jacksonville, FL 32216. Phone: 904-296-9075; Fax:
904-296-5499; E-mail: gonwa.thomas@mayo.edu
Copyright © 2006 by the American Society of Nephrology

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 and progresses with worsening of
the liver disease (7). Theunderlying 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 kidney
function associated with severe renal vasoconstriction and...