What is the management approach for hepatorenal syndrome?

Management of Hepatorenal Syndrome

Terlipressin plus albumin is the first-line pharmacological treatment for hepatorenal syndrome, with liver transplantation being the definitive treatment. 1, 2

Diagnostic Approach

• Diagnosis requires excluding other causes of acute kidney injury in cirrhotic patients with:

  • Advanced cirrhosis with ascites
  • Serum creatinine >1.5 mg/dL
  • No improvement after at least 2 days of diuretic withdrawal and volume expansion with albumin
  • Absence of shock
  • No current/recent nephrotoxic drug exposure
  • Absence of parenchymal kidney disease 1

• Diagnostic paracentesis should be performed to rule out spontaneous bacterial peritonitis, which can precipitate HRS 1, 2

Pathophysiology

• Four key factors contribute to HRS development:
  • Splanchnic vasodilation causing reduced effective arterial blood volume
  • Activation of sympathetic nervous system and renin-angiotensin-aldosterone system
  • Impaired cardiac function due to cirrhotic cardiomyopathy
  • Increased synthesis of vasoactive mediators affecting renal blood flow 3

First-Line Pharmacological Treatment

• Terlipressin plus albumin is the first-line treatment with 40-50% effectiveness rate 3, 1, 2

  • Initial dose: 1 mg IV every 4-6 hours
  • Increase stepwise to maximum 2 mg every 4 hours if serum creatinine doesn't decrease by at least 25% after 3 days
  • Continue until serum creatinine decreases below 1.5 mg/dL 3, 1

• Albumin administration:

  • 1 g/kg on day 1 (maximum 100g)
  • Followed by 20-40 g/day 4, 2

Alternative Treatments (Where Terlipressin Unavailable)

• Norepinephrine plus albumin:

  • Starting dose: 0.5 mg/h
  • Increase every 4 hours by 0.5 mg/h to maximum 3 mg/h
  • Goal: Increase mean arterial pressure by 10-15 mmHg or urine output >50 mL/h
  • Similar efficacy to terlipressin but requires ICU monitoring 2

• Midodrine plus octreotide plus albumin:

  • Midodrine: Titrate to 12.5 mg orally three times daily
  • Octreotide: 200 μg subcutaneously three times daily
  • Albumin: 10-20 g IV daily for up to 20 days
  • Less effective than terlipressin or norepinephrine 1, 2

Definitive Treatment

• Liver transplantation is the definitive treatment for both type 1 and type 2 HRS 1, 2
  • Expedited referral recommended for patients with type 1 HRS
  • Post-transplant survival rates approximately 65% 1
  • Treatment of HRS before transplantation may improve post-transplant outcomes 1

Other Treatment Options

• Transjugular intrahepatic portosystemic shunt (TIPS):

  • May improve renal function in selected patients with type 2 HRS
  • Limited evidence for type 1 HRS 1, 2

• Renal replacement therapy:

  • Consider as bridge to liver transplantation in patients unresponsive to vasoconstrictor therapy 1, 2

Prevention of HRS

• Norfloxacin (400 mg/day) reduces HRS incidence in advanced cirrhosis 1
• Pentoxifylline (400 mg three times daily) prevents HRS development in severe alcoholic hepatitis 1
• Albumin administration during spontaneous bacterial peritonitis and after large volume paracentesis 1, 5

Monitoring and Response Assessment

• Parameters to monitor:

  • Urine output
  • Fluid balance
  • Arterial pressure
  • Standard vital signs
  • Central venous pressure (ideally) 3

• Response is characterized by:

  • Progressive reduction in serum creatinine
  • Increase in arterial pressure
  • Increase in urine volume and serum sodium 2

Important Considerations and Pitfalls

• Discontinue albumin when anasarca (severe peripheral edema) develops 4
• Patients with serum creatinine >5 mg/dL are unlikely to benefit from terlipressin 6
• Adverse effects of vasoconstrictors include cardiac or intestinal ischemia, pulmonary edema, and distal necrosis 2
• The reduction in serum creatinine after treatment should not change the decision to perform liver transplantation since prognosis after HRS recovery remains poor 1