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REFERAT

HEPATORENAL SYNDROME
PEMBIMBING

: dr. Sahala Panggabean SpPD KGH

PRESENTAN

: Ilham Suryo Wibowo Antono

History
1863:
Absence of histological changes to
the kidney in some cirrhotics with renal failure
1956:
1st detailed description of the
syndrome by Hecker and Sherlock
1960s:
Reversal of renal failure with kidney
transplant to patients with CKD
1970s:
Reversal of HRS with liver
transplantation

Hepatorenal Syndrome
Hepatorenal Syndrome is a severe complication of
end stage liver disease associated with an 80%95% mortality at 2 weeks.
The only interventions that have been shown to
improve survival are liver transplantation and
more recently the vasopressin analogues and TIPS
Type 1 (Acute)
Type 2 (Chronic)

Epidemiology
Incidence
7-10% in hospitalized cirrhotics with ascites
20% at 1 year, 40% at 5 years

Risk Factors
Advanced ascites (diuretic resistant)
Large volume paracentesis w/o albumin (15%)
SBP (20%)

Prognosis
Worst prognosis of all complications of cirrhosis
Type 1 median survival: <2 weeks
Type 2 median survival: ~6 months

Diagnosis
Lack of specific testing
Diagnosis of exclusion
Differential Diagnosis of renal failure in cirrhosis

Hypovolaemia (GI hemorrhage, shock)


Nephrotoxins (drugs, contrast)
Glomerulonephritis (Hep B and C)
Acute Tubular Necrosis
Obstruction

Diagnostic Criteria
Major Criteria

Chronic or acute liver disease with advanced liver failure or portal


hypertension

Low GFR (Cr > 132mol/L OR CrCl < 40mL/min)

Exclusion of shock, ongoing bacterial infection, volume depletion, and


use of nephrotoxic drugs

No improvement in renal function despite stopping diuretics and volume


repletion with 1.5L of saline

No proteinuria or ultrasonographic evidence of obstruction or


parenchymal renal disease
Arroyo et al; Hepatology 1996; 23: 164-76

Diagnostic Criteria
Minor Criteria

Urine volume < 500mL/day

Urine sodium < 10mEq/L

Urine osmolality > plasma osmolality

Urine RBCs < 50 per hpf

Serum sodium < 130mEq/L


Arroyo et al; Hepatology 1996; 23: 164-76

Pathophysiology
Splanchnic arteriolar vasodilatation

Decreased effective arterial volume (EAV)


Decreased systemic vascular resistance
Hypotension
Activation of vasoconstrictor systems
Renin-Angiotensin Angiotensin-AldosteroneSystem
Sympathetic Nervous System
Anti-Diuretic Hormone

Pathophysiology of CLD
Portal Hypertension
Peripheral and splanchnic arterial dilatation
Reduced effective blood volume

NSAID
Aminoglycosides
Diuretics
Sepsis

Activation of renin-angiotensin-aldosterone systemRenal vasoconstriction


Sympathetic nervous system
Reduced GFR
ADH
HRS
Na retention
&
Water retention

Ascites and Oedema


Low urinary Na
Dilutional hyponatraemia

Plasma volume expansion


Ascites
Schrier et al Hepatol 1988

Pathophysiology
Hyperdynamic circulation
Hypotension from reduced effective art
vol
Low systemic vascular resistance (SVR)
Baroreceptor activation
SNS activation leading to increased
contractility
Increased cardiac output

Treatment of HRS
Vasoconstrictors
Often combined with albumin
Vasopressin analogues (Terlipressin)

TIPS
Liver Transplantation

REMEMBER!

VASOKONSTRIKTOR

ALBUMIN

Terlipressin
Synthetic vasopressin analogue
Most studied drug for treatment of HRS
Mechanism: V-1 receptor agonist
Splanchnic vasoconstriction
Adverse events (arrhythmia, ischemia)
<5%
IV bolus dosing

Pathophysiology of CLD
Portal Hypertension
Peripheral and splanchnic arterial dilatation

Vasopressin

Reduced effective blood volumeIncreased blood vol

Activation of renin-angiotensin-aldosterone systemRenal vasoconstriction


Sympathetic nervous system
Reduced GFR
ADH
HRS
Na retention
&
Water retention

Ascites and Oedema


Low urinary Na
Dilutional hyponatraemia

Plasma volume expansion


Ascites
Schrier et al Hepatol 1988

Terlipressin in HRS

Meta-analysis: terlipressin therapy for the hepatorenal syndrome


F. Fabrizi, V. Dixit & P. Martin APT 2006 24:935-44

Terlipressin in HRS
The pooled rate of patients who reversed hepatorenal
syndrome after terlipressin therapy was
0.52 (95% CI, 0.42; 0.61), P =0.0001; I2=

24.6%.

The pooled frequency of responder patients who showed


hepatorenal syndrome recurrence after terlipressin
withdrawal was
0.55 (95% CI, 0.40; 0.69), P =0.00001; I2=

44.3%.

Meta-analysis: terlipressin therapy for the hepatorenal syndrome


F. Fabrizi, V. Dixit & P. Martin APT 2006 24:935-44

Six randomised trials were eligible for inclusion


3 trials (total 51 patients) assessed terlipressin 1 mg bd for 2 to 15 days
Co-interventions included albumin, fresh frozen plasma, and cimetidine
Terlipressin reduced mortality rates by 34%
The control group mortality rate was 65%
Terlipressin improved renal function assessed by creatinine clearance,
serum creatinine and urine output
2009

TIPS

Reduce portal hypertension


Increase effective arterial volume
Reverse splanchnic vasodilatation
Complications
Encephalopathy
Shunt stenosis
Haemolysis
Hyperbilirubinaemia

Liver Transplantation
Treatment of choice for HRS
Limited by organ availability and mortality of HRS
Higher rate of complications:
Higher post operative mortality
More days in the ICU
Increased need for post-op RRT

Improvement in renal function


Increased GFR post-op vs. decline in non-HRS
Lower overall GFR compared to non HRS

Thank You

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