Hepatorenal syndrome

How is HRS defined?

• HRS is a distinct form of acute or

subacute renal failure characterized
by severe renal vasoconstriction,
which usually develops in
decompensated cirrhosis or acute
liver failure( ALF)
 Revised diagnostic hepatorenal
syndrome criteria in liver disease
• Liver disease with ascites.
• Serum creatinine >133 μmol/l (1.5 mg/dl). CCl exluded.
• No improvement of sr cr after at least 2 days with
diuretic withdrawal + volume expansion with albumin
at 1 g/kg of body weight per day up to a max of 100 
g/day.Albumin is preferred plama volume expander.
• Absence of shock. Ongoing bacterial infection without
shock may be HRS.
• No current or recent treatment with nephrotoxic drugs.
• *Absence of parenchymal kidney disease as indicated
by proteinuria >500 mg/day, microhematuria (>50 red
blood cells /HPF) and/or abnormal renal US.
 Types of HRS
Type I
• Severe and rapidly progressive renal failure
• Doubling of sCr to  2.5 mg/dL in  2 weeks
• Usually precipitated by GI hemorrhage, surgery, acute
hepatitis etc but can occur spontaneously
• Occurs in 30 % of patients with SBP despite resolution of
infection
• Poor prognosis: median survival time of 2 weeks after
onset

Arroyo Vet al consensus statement

 Types of HRS
Type 2
• Moderate and steady decline in renal function:
sCr  2.5 mg/dL
• Less severe liver failure and hypotension than
with Type I HRS
• Characterized by severe ascites which is diuretic-
resistant
• Often evolves into Type I HRS following insult
• Prognosis: median survival time of 6 months
after onset
The pathophysiology of the
hepatorenal syndrome
 Mediators of Vasodilation
• NO
•  in cirrhosis
• Stimulated by endotoxemia and increased shear
steress in the systemic and splanchic circulation.
• Renders splanchnic circulation resistant to
vasopressors

• Glucagon
• Desensitizes splanchnic circulation to
catecholamines and AII
• Direct Vasodilator
• cAMP levels thereby  NO synthesis
 Role ofRoleaofprecipitating factor in HRS
a precipitating factor in HRS.

Wadei H©2006
M byetAmerican
al. CJASN 2006;1:1066-1079
Society of Nephrology
 Treatment of the Hepatorenal syndrome

• Volume expanders and vasoconstrictors

• Transjugular Intrahepatic Portocaval Shunt
(TIPS)
• Liver transplantation
• Molecular adsorbent recycling system
(MARS)
General Measures
• Diuretics and nephrotoxic agents stopped
• Rx infection and GI bleeding
• Especially in type 1 HRS, adrenal function should be
tested with ACTH stim test and treated with steroids
if indicated
• Assess intravascular volume status
• Massive ascites may impair renal vein outflow, if
tense ascites is present, check bladder pressures
and paracentesis with albumin replacement is
performed
 Albumin is important in cirrhosis

• Improves circulatory dysfunction in cirrhosis by

expanding central blood volume and increasing
cardiac output
• Albumin has a domain with ability to stabilize free
radicals
• Albumin alleviates splanchnic arterial
vasodilation thereby increasing BP probably
attributable to the ability of albumin to bind
vasodilators
 Role of albumin in HRS
Albumin
Infusion
Improvement
Intravascular
in circulating
volume
albumin
expansion
function
Increased
Increased antioxidant
cardiac activity,
preload decreased NO

Improvement Increased SVR

in LVF Improvement
of circulatory
dysfunction
 Indications for albumin
• Large Volume Paracentesis ( >5L)-
Albumin 8-10gms/L
• SBP
• HRS 1-With terlipressin
• Diagnosis of HRS 1-1.5 g/kg of 20%
albumin

Mattos et al, Annals of Hepatology 10, 2011,S15-20

 Vasoconstrictors

• Vasoconstrictors and albumin are recommended as

the first line of treatment for type‐1 HRS.
• Terlipressin is the most widely used vasoconstrictor.
• With the use of terlipressin (2–12 mg/day) and albumin
(20–40 g/day after 1 g/kg on the first day), about 60% of
renal failure cases recover.
• Reversal of HRS improves survival and increases
chance of liver transplantation
 TIPS
Transjugular intrahepatic
portosystemic shunts
• A low-resistance channel between hepatic
vein and the intrahepatic portion of the
portal vein (usually the right branch) using
angiography
• Tract kept patent by deployment of an
expandable metal stent
• Returns blood to systemic circulation and
reduces portal hypertension
 Extracorporeal albumin dialysis(ECAD)
Molecular adsorbent recycling system (MARS)
• Cell free, modified dialysis technique using
albumin enriched dialysate and CRRT.
• Extracorporeal liver support system designed to
remove albumin-bound substances
• Hypothesis:
Removal of albumin bound and water soluble
substances substances will stabilize liver and
renal function
• NO transported primarily bound to serum albumin
as an S-nitrosthiol
Cholestyramine Activated charcoal
anion exchanger adsorber

Mitzner S, et al. Liver transplantation 2000:6;

277-286
Mitzner S, et al. Liver transplantation 2000:6;
277-286
Liver Transplantation
 Liver Transplantation

• Patients with types 1, 2 HRS should undergo

evaluation for liver transplantation. Patients with
type 1 HRS are on priority for transplant and
despite this, not transplanted because of
underlying precipitating factor.
• Liver transplantation is more practical and
successful in type 2 HRS, because of an absence
of precipitating events and relatively less severe
renal failure.
THANK YOU