Transcript hepatorenal syndrome

This lecture was conducted during the Nephrology
Unit Grand Ground by Medical Student rotated under
Nephrology Division under the supervision and
administration of Prof. Jamal Al Wakeel, Head of
Nephrology Unit, Department of Medicine and Dr.
Abdulkareem Al Suwaida, Chairman of the
Department of Medicine. Nephrology Division is not
responsible for the content of the presentation for it is
intended for learning and /or education purpose only.
Presented by:
Adel Al Mudaibegh
Medical Student
February 2009

Refers to the development of acute renal failure
in a patient who usually has advanced liver
disease due to:
o cirrhosis
o severe alcoholic hepatitis
o metastatic tumor (less often)

Can occur in a substantial proportion of patients
with fulminant hepatic failure from any cause.

The hepatorenal syndrome usually represents
the end-stage of a sequence of reductions in
renal perfusion induced by increasingly severe
hepatic injury.

It is a prerenal disease, as the kidneys are
histologically normal.
INCIDENCE

Incidence of 10% among hospitalized patients
with cirrhosis and ascites.

Equal in both sexes.

All people with CLD are at risk for HRS.

4th to 8th decades of life.
PATHOGENESIS

Splanchnic vasodilatation appears to play an
important role in the decline in renal function in
hepatic disease.

Progressive  in cardiac output &  in SVR
despite local increments in renal & femoral
vascular resistance from induction of RAS &
sympathetic systems.

May be in part due to nitric oxide.

 in Renal Perfusion is assoc. with  in GFR and
Na+ excretion, as well as a  in MAP.

Other suspects include an  in ratio of
vasoconstrictor thromboxanes / vasodilator
prostaglandins.

Arterial vasodilation theory:
Proposes that HRS is the result of the effect of
vasoconstrictor systems acting on the renal
circulation and activated as a homeostatic
mechanisms to improve the extreme
underfilling of the arterial circulation .That
leads to decreased renal perfusion and
glomerular filtration rate (GFR) but tubular
function is preserved.
Liver cirrhosis & PHT
Splanchnic VD
Decreased effective ABV
Increased VC systems
Renal Vasoconstriction
Systemic VC
HRS
ESTIMATION OF RENAL
FUNCTION

The reduction in GFR in patients with hepatic
disease is often masked clinically.

Both urea and creatinine production may be
substantially reduced due to the liver disease
and to ↓ muscle mass and ↓ protein and meat
intake (plasma creatinine may appear to be
within the normal range (1 to 1.3 mg/dL or 88.4
to 115 µmol/L).

The BUN is variable. It may be lower than
expected from the GFR if urea production is
reduced or it may be elevated, out of proportion
to the plasma creatinine concentration, if urea
production is adequate.

GFR more accurately measured by 24-hr
creatinine clearance to demonstrate  in
production.
CLINICAL PRESENTATION
Oliguria
 Generally benign urine sediment
 Very low rate of sodium excretion
 Progressive rise in the plasma creatinine
concentration

Types of Hepatorenal Syndrome:

Based upon the speed of onset of renal
failure, two forms of hepatorenal syndrome
have been described:
 Type I hepatorenal syndrome (more serious
type)
 Type II hepatorenal syndrome (less severe)

Type I hepatorenal syndrome:
At least a 50% lowering of the creatinine
clearance to a value below 20 mL/min in less
than a two week period or
 At least a twofold increase in serum creatinine
to a level greater than 2.5 mg/dL (221 µmol/L).


Commonly oliguric.

Median survival time is only 2 weeks.

Type II hepatorenal syndrome:

Characterized by ascites that is resistant to
diuretics.

Less severe than type I.

Associated with relatively preserved liver
function.

Median survival time is about 6 months.
Precipitants
GI bleeding
 Infection (Spontaneous bacterial peritonitis)


Diuretics can cause azotemia, this improves
with cessation of therapy and fluid repletion. In
comparison, the HRS worsens, even after
diuretics are stopped.
DIAGNOSTIC CRITERIA
1)
Chronic or acute hepatic disease with
advanced hepatic failure and portal
hypertension.
2)
Plasma creatinine concentration >1.5 mg/dL
(133 µmol/L) that progresses over days to
weeks.
3)
The absence of any other apparent cause
(paranchymal renal disease, shock, ongoing
infection, obstruction, nephrotoxic medications).
4)
Proteinuria < 500 mg/day.
5)
Lack of improvement in renal function after
volume expansion with IV albumin (or 1.5 L of
isotonic saline) for at least two days and
withdrawal of diuretics.

Additional criteria:
○ Urine red cell excretion < 50 cells per high
power field
○ Urine volume < 500 mL/d
○ Urine sodium level <10 mEq/L
○ Urine osmolality > plasma osmolality
○ Serum sodium concentration <130 mEq/L
Diagnosis

The diagnosis of the hepatorenal syndrome
is one of exclusion.

Both glomerulonephritis and vasculitis can
occur in patients with liver disease and
should be suspected in patients with an
active urine sediment containing red cells
and red cell and other casts.
 It
is particularly important to exclude
spontaneous bacterial peritonitis,
which is complicated by acute renal
failure that may be reversible in 30 to
40% of patients.
DDx

Acute tubular necrosis
Patients with cirrhosis may develop ATN after
 a course of aminoglycoside therapy
 the administration of a radiocontrast agent
 an episode of sepsis or bleeding.
The following criteria may be useful for diagnosis:
 ↑urine sodium conc.
 fractional excretion of sodium above 2%
 granular & epithelial cell casts in the urine
sediment.
 Urine/serum osmolarity ratio<1

Prerenal disease
Decreased renal perfusion can also be induced
by:
 Gastrointestinal losses or bleeding.
 Shock.
 Therapy with a diuretic or a NSAID.
TREATMENT
 Liver
transplant:
o
The ideal treatment of HRS is liver
transplantation.
o
Long-term survival rates are excellent, with the
survival rate at 3 years approaching
approximately 60%.
o
Effective alternative therapies to increase survival
chances for patients with HRS are urgently
needed until transplantation can be performed.
 Medical

treatment:
IV sympatholytic agent clonidine
 In early stages can raise the GFR by as
much as 25%.
 Lowering renal sympathetic tone and
renal vascular resistance.
 This benefit does not appear to be
sustained with chronic oral therapy.

Midodrine and octreotide

Combination therapy with midodrine (a selective
alpha-1 adrenergic agonist) and octreotide (a
somatostatin analog) may be highly effective
and safe.

Since midodrine is a systemic vasoconstrictor
and octreotide is an inhibitor of endogenous
vasodilator release, combined therapy would
improve renal and systemic hemodynamics.

Treatment with midodrine & octreotide was
associated with:
 Significant reduction in mortality and
 Significantly higher incidence of a reduction
in serum creatinine concentration to less than
1.5 mg/dL (133 µmol/L).

Norepinephrine plus albumin

Showed a reduction in serum creatinine
concentration.

Also provides significant blood pressure
support.

Other therapies:

Vasopressin analougs (ornipressin and
terlipressin)
 reduce splanchnic vasodilation
 When administered with circulating volume
expansion there was an increase in GFR &
improved renal function.

Prostaglandin analog, misoprostol.

N-acetylcysteine.

ACE inhibitors.
Tried with conflicting evidence of benefit,
or evidence of harm. So cannot be
recommended.

Transjugular intrahepatic portosystemic
shunt (TIPS):

Insertion of TIPS was associated with a gradual
improvement in glomerular filtration rate.

TIPS may provide short-term benefit.

Given the risks associated with this procedure
(particularly the high incidence of
encephalopathy), it should be considered only
as a last resort in patients who are not a
candidate for or are awaiting liver
transplantation.

Peritoneovenous shunt

Insertion of a peritoneovenous shunt can
improve systemic hemodynamics and modestly
reduce the plasma creatinine concentration.

However, survival is not improved and
complications limit use of this procedure.

Have no role in type I HRS

Dialysis

Patients with hepatorenal syndrome who
progress to renal failure can be treated with
dialysis.

Most commonly done when patients are
awaiting a liver transplant or when there is the
possibility of improvement in liver function.

In addition, dialysis improves the priority score
for the transplant.
Treatment summary:

Combination therapy with midodrine and
octreotide or single agent therapy with
norepinephrine should be considered in
patients with HRS.

Also administer IV albumin at approximately 1
g/kg per day (100 g maximum) for two or more
days.

Liver transplant candidates who develop endstage renal disease usually undergo
hemodialysis.
PROGNOSIS

Overall, the mortality of patients with liver
failure is substantially worse if they develop
hepatorenal syndrome.

The outcome of patients with hepatorenal
syndrome is strongly dependent on
reversal of the hepatic failure.
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