Hepatorenal Syndrome

Pre-renal failure secondary to renal vasoconstriction in the setting of systemic and splanchnic vasodilatation in the setting of advanced cirrhosis that is:

• Secondary to severe chronic liver disease
  Usually with portal hypertension.
• Unresponsive to fluid therapy
• Divided into two subtypes
  • Type 1
    Rapidly progressive.
  • Type 2
    Progressive deterioration.
• Related to the progression of portal hypertension, rather than the progression of the hepatic lesion
• Occurs due to fall in renal perfusion pressure due to systemic vasodilation
  • Progressive splanchnic vasodilation results in splanchnic blood volume sequestration and ↑ RAAS activity
  • Note that the kidneys are usually functional and intact
    Renal function will return if portal hypertension is resolved (i.e. liver transplantation, or transplantation of the kidneys to a new host).
• Indicative of poor prognosis

Pathophysiology

• Hepatic dysfunction leads to drastic splanchnic NO overproduction and splanchnic vasodilation
  Circulating volume is sequestered in the dilated splanchnic circulation.
• RAAS activation occurs in the setting of apparent hypovolaemia
  • ↑ Renin constricts afferent arteriole and ↓ renal perfusion
  • Systemic vasoconstrictor release does not overcome splanchnic NO production
    
    • There is a global ↓ in SVR and ↑ in CO
    • Progressively more volume is sequestered in the splanchnic circulation
    • Renal perfusion suffers due to ↓ SVR and ↑ afferent arteriolar constriction
• Ascites
  High volume ascites contributes to ↑ IAP and compression of the kidney.

Aetiology

Often insidious, but acute decline is usually precipitated by another renal-failure inducing event:

The difference between “AKI secondary to NSAID/” and “hepatorenal syndrome secondary to hypovolaemia” is the reversibility.

If the AKI recovers after volume administration, then it was standard pre-renal failure; if it doesn’t, then it’s hepatorenal syndrome.

• Volume loss
  • Large paracentesis without albumin replacement
  • Diuresis
  • Bleeding
• Infection
  • SBP
  • Sepsis
• Nephrotoxins

Clinical Manifestations

Constellation of:

• Biochemical renal failure
• Minimal proteinuria
• Low sodium excretion
  Urinary Na <10mmol/L.
• Oliguria or normal urine output
  Especially early.

Diagnostic Approach and DDx

Diagnosis requires all of:

Diagnosis of hepatorenal syndrome essentially requires:

• Cirrhosis with ascites
• Renal impairment
  Without other cause, i.e. despite:
  • Diuretic withdrawal
  • Volume resuscitation
  • Nephrotoxin cessation
  • Absence of shock
  • Absence of parenchymal disease
    No haematuria, proteinuria, normal sonographic appearance.

• Renal failure
  • Creatinine >150mmol/L
  • Non-responsive to fluid and albumin resuscitation
• Chronic liver disease
  • Ascites
  • Cirrhosis
• Absence of another cause:
  • Nephrotoxins
  • Intra-renal disease
    i.e. No:L
    • Proteinuria
    • Microhaematuria
    • Sonoanatomical renal abnormality

Other differentials include:

• Pre-renal failure
  • Cessation of beta-blockade
• ATN

Management

• Restore renal blood flow and perfusion pressure
  • Vasopressors
  • Albumin

Resuscitation:

• C
  • Volume
    20% albumin:
    • 1-1.5g/kg on day 1 and 2
    • 20-40g/day thereafter
  • Systemic vasoconstrictors
    Aim ↑ MAP by 10-15mmHg above presentation (at least >80mmHg).
    • Discontinue anti-hypertensives
    • Predominantly noradrenaline
    • Midodrine safe and effective
  • Splanchnic vasoconstrictors
    • Terlipressin
      1-2mg IV Q4-6H.
    • Octreotide
      100ug SC Q8H or 50ug/hr IV infusion.
• G
  • Ascitic drainage
    Relieve abdominal compartment syndrome.

Specific therapy:

• Procedural
  • TIPS
    ↓ Ascites production.
  • Liver transplantation

Prognosis

Indicative of very high mortality without liver transplantation.

Key Studies

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References