Absence of histological changes to the kidney in some cirrhotics with renal failure 1863: Absence of histological changes to the kidney in some cirrhotics with renal failure

1863: Absence of histological changes to the kidney in some cirrhotics with renal failure

• 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

Functional renal failure

• 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 is a severe complication of end stage liver disease associated with an 80%-95% mortality at 2 weeks.

• 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)

Type 1

• 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%)

Type 2

• Type 2

• Slower decline in renal function

• Criteria for type 1 HRS not met

• Development of diuretic resistant or refractory ascites

Incidence

• 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

Lack of specific testing

• 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

Major 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

• 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

Minor 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

Splanchnic arteriolar vasodilatation

• 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

Hyperdynamic circulation

• Hyperdynamic circulation

• Hypotension from reduced effective art vol

• Low systemic vascular resistance (SVR)

• Baroreceptor activation

• SNS activation leading to increased contractility

• Increased cardiac output

Vasoconstrictors

• Vasoconstrictors

• Often combined with albumin
• Vasopressin analogues (Terlipressin)

• TIPS

• Liver Transplantation

Synthetic vasopressin analogue

• 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

Reduce portal hypertension

• Reduce portal hypertension

• Increase effective arterial volume

• Reverse splanchnic vasodilatation

• Complications

• Encephalopathy
• Shunt stenosis
• Haemolysis
• Hyperbilirubinaemia

Treatment of choice for HRS

• 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

• Thank You