Basic approach to Hepatorenal Syndrome

1. By Dr. Nauman Zafar
PGR Medicine

2.  Introduction
 Pathogenesis
 Clinical Presentation
 Types
 Precipitants
 Diagnosis
 Differential Diagnosis
 Treatment
 Prevention
 Prognosis

3.  The hepatorenal syndrome represents the
end-stage of a sequence of reductions in
renal perfusion induced by increasingly
severe hepatic injury
 It is one of many potential causes of acute
kidney injury in patients with acute or chronic
liver disease
 The hepatorenal syndrome is a diagnosis of
exclusion
 It is associated with poor prognosis

4.  Arterial vasodilatation in the splanchnic circulation
due to portal hypertension and Increased
production or activity of vasodilators
 Low effective arterial blood volume
 Cirrhotic cardiomyopathy
 Hypotension-induced activation of the RAAS
 Increases in renal and femoral vascular resistance
 The decline in renal perfusion and reductions in
GFR and sodium excretion

7. In patient with advanced chronic liver disease
who have portal hypertension and ascites and
occasionally fulminant hepatitis

8.  A progressive rise in serum creatinine
 An often normal urine sediment
 No or minimal proteinuria (less than 500 mg
per day)
 A very low rate of sodium excretion (ie, urine
sodium concentration less than 10 meq/L)
 Oliguria (may not be present in initial stages)
[1]

9.  Type 1 hepatorenal syndrome
 Type 2 hepatorenal syndrome

10.  More serious type
 At least a twofold increase in serum
creatinine (reflecting a 50 percent reduction
in creatinine clearance)
 Creatinine level rises to greater than 2.5
mg/dL (221 micromol/L)
 During a period of less than two weeks

11.  Less severe than type 1 disease.
 The major clinical feature in patients with
type 2 hepatorenal syndrome is ascites that is
resistant to diuretics
 Median survival of approximately six
months
[1]

12.  The onset of renal failure is typically
insidious but can be precipitated by an acute
insult, such as bacterial infection ( e.g.
spontaneous bacterial peritonitis) or
gastrointestinal bleeding
 Diuretics do not cause hepatorenal syndrome

13.  Chronic or acute hepatic disease with
advanced hepatic failure and portal
hypertension
 A serum creatinine above 1.5 mg/dL (133
micromol/L) that progresses over days to
weeks

14.  The absence of any other apparent cause for
the acute kidney injury, including shock,
current or recent treatment with nephrotoxic
drugs, and the absence of ultrasonographic
evidence of obstruction or parenchymal renal
disease

15.  Urine red cell excretion of less than 50 cells
per high power field (when no urinary
catheter is in place) and protein excretion
less than 500 mg/day
 Lack of improvement in renal function after
volume expansion with intravenous albumin
(1 g/kg of body weight per day up to 100
g/day) for at least two days and withdrawal of
diuretics

16.  Kidney injury associated with infection (such
as sepsis or spontaneous bacterial peritonitis)
– 46 percent
 Prerenal acute kidney injury – 32 percent
 Hepatorenal syndrome – 13 percent
 Parenchymal renal disease (such as
glomerulonephritis) – 9 percent

17. Ideal treatment:
 Improvement of liver function from recovery
of alcoholic hepatitis
 Treatment of decompensated hepatitis B with
effective antiviral therapy
 Recovery from acute hepatic failure
 Liver transplantation

18.  Best treatment for both type1 and type 2 HRS
 Treats the underlying organ dysfunction that
triggers the pathophysiologic pathway to HRS
 Drastically improve survival
 2 and 5 year survival rates of 73.8% and
67.1% respectively
[3]
[2]

19. Supportive treatment:
Pharmacological
 Terlipressin with albumin
 Norepinephrin with albumin
 Midodrine and octreotide with albumin
TIPS
Dialysis

20. Terlipressin with albumin
 Terlipressin is given as an intravenous bolus
(1 to 2 mg every four to six hours)
 Albumin is given for two days as an
intravenous bolus (1 g/kg per day [100 g
maximum]), followed by 25 to 50 grams per
day until terlipressin therapy is discontinued

21. Norepinephrin with albumin
 Norepinephrine is given intravenously as a
continuous infusion (0.5 to 3 mg/hr) with the
goal of raising the mean arterial pressure by
10 mmHg
 Albumin is given for at least two days as an
intravenous bolus (1 g/kg per day [100 g
maximum])

22. Midodrine and octreotide with albumin
 Midodrine is given orally (starting at 7.5 mg
and increasing the dose at eight-hour
intervals up to a maximum of 15 mg by
mouth three times daily),
 Octreotide is either given as a continuous
intravenous infusion (50 mcg/hr) or
subcutaneously (100 to 200 mcg three times
daily)

23.  Albumin is given for two days as an
intravenous bolus (1 g/kg per day [100 g
maximum]), followed by 25 to 50 grams per
day until midodrine and octreotide therapy is
discontinued

24.  A fall in the serum creatinine to below 1.5
mg/dL
 39 to 59 percent for terlipressin therapy
 43 to 58 percent for norepinephrine therapy
 40 percent for midodrine and octreotide
therapy
[1]
[1]
[1]

25.  For patients with partial response (serum
creatinine does not decrease <1.5 mg/dl) or
in those patients without reduction of serum
creatinine treatment should be discontinued
within 14 days
[2]

26. TIPS
 In highly selected patients who fail to
respond to medical therapy with the above
regimens and who are considered well
enough to undergo the procedure
Dialysis
 Hemodialysis or continuous venous
hemofiltration dialysis can be used as a
bridge to liver transplantation or liver
recovery

27. Albumin
 In patients with SBP, the administration of
intravenous albumin (1.5 g/kg) at the time of
diagnosis of infection and another dose of
albumin (1 g/kg) on day 3 of antibiotic
treatment reduces the incidence of both renal
impairment and mortality

28. Norfloxacin
 400 mg/day decreases the incidence of HRS
in advanced cirrhosis
Pentoxifylline
 Some data to suggest that treatment with
pentoxifylline (1200 mg/day) decreases the
incidence of HRS in patients with severe
alcoholic hepatitis and advanced cirrhosis

29.  The mortality of patients with liver failure is
substantially worse if they develop
hepatorenal syndrome
 Without therapy, most patients die within
weeks of the onset of the renal impairment

30.  The outcome of patients with hepatorenal
syndrome, as well as recovery of kidney
function, is strongly dependent upon reversal
of the hepatic failure, whether spontaneous,
following medical therapy, or following
successful liver transplantation

31. http://www.uptodate.com/contents/hepatoren
al-syndrome
EASL clinical practice guidelines on the
management of ascites, spontaneous bacterial
peritonitis, and hepatorenal syndrome in
cirrhosis 2010
http://www.medscape.com/viewarticle/71059
1
[1]
[2]
[3]