Transcript Hepatorenal Syndrome

Hepatorenal Syndrome
Dr Allister J Grant
Leicester Liver Unit
http://hepatologist.eu
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
Definition of HRS
• Functional renal failure
– Absence of Histological changes
• Occurs in patients with chronic liver disease
• Progressive liver failure and ascites
• Can occur acutely in certain settings
– Spontaneous bacterial peritonitis
– Large volume paracentesis without albumin
• Marked renal vasoconstriction
• Reduced GFR
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)
Clinical Types of HRS
• Type 1
• Rapid decline in renal function
• Doubling of serum Cr >132 or reduction in 24h
CrCl to <40ml/min
• Less than 2 weeks
• Spontaneous
• Associated with SBP (20%) or large volume
paracentesis w/o albumin (15%)
Clinical Types of HRS
• Type 2
• Slower decline in renal function
• Criteria for type 1 HRS not met
• Development of diuretic resistant or refractory
ascites
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
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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 > 132mol/L OR CrCl < 40mL/min)
•
Exclusion of shock, ongoing bacterial infection, volume depletion, and use of
nephrotoxic drugs
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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-Aldosterone-System
– Sympathetic Nervous System
– Anti-Diuretic Hormone
Pathophysiology
Hyperdynamic circulation
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Hypotension from reduced effective art vol
Low systemic vascular resistance (SVR)
Baroreceptor activation
SNS activation leading to increased
contractility
• Increased cardiac output
Pathophysiology of CLD
Portal Hypertension
NSAID
Aminoglycosides
Diuretics
Sepsis
Peripheral and splanchnic arterial dilatation
Reduced effective blood volume
Activation of renin-angiotensin-aldosterone system
Sympathetic nervous system
ADH
NaCl
Renal vasoconstriction
Reduced GFR
HRS
Na retention
&
Water retention
Ascites and Oedema
Low urinary Na
Dilutional hyponatraemia
Plasma volume expansion
Ascites
Schrier et al Hepatol 1988
Treatment of HRS
• Vasoconstrictors
– Often combined with albumin
– Vasopressin analogues (Terlipressin)
• TIPS
• Liver Transplantation
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
Vasopressin
Peripheral and splanchnic arterial dilatation
Reduced effective blood volume
Increased blood vol
Activation of renin-angiotensin-aldosterone system
Sympathetic nervous system
ADH
Renal vasoconstriction
Reduced GFR
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
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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 (35% vs. 5% w/o HRS)
• Improvement in renal function
– Increased GFR post-op vs. decline in non-HRS pts
– Lower overall GFR compared to non HRS pts
Thank You