What is the treatment for hepatorenal syndrome?

Treatment of Hepatorenal Syndrome

The first-line treatment for hepatorenal syndrome should be a combination of vasoactive drugs (terlipressin, or the combination of midodrine and octreotide) plus albumin infusion, with expedited referral for liver transplantation as the definitive treatment. 1

Types of Hepatorenal Syndrome

Hepatorenal syndrome (HRS) is classified into two types:

• Type 1 HRS: Rapidly progressive reduction in renal function with doubling of serum creatinine to >2.5 mg/dL in less than 2 weeks. Median survival without treatment is approximately 2 weeks.
• Type 2 HRS: More stable kidney failure without rapid progression. Median survival is approximately 6 months. 1

Treatment Algorithm

First-Line Pharmacological Treatment:

1. Volume expansion with albumin:

   • Initial dose: 1 g/kg body weight/day (maximum 100 g/day)
   • Continue for at least 2 days before confirming HRS diagnosis 1

2. Vasoconstrictor therapy (choose one option):

   Option A: Terlipressin plus albumin (preferred if available):

   • Dosing: 0.85 mg IV every 6 hours
   • Mechanism: Vasopressin V1 receptor agonist that increases renal blood flow by reducing portal hypertension and increasing mean arterial pressure 2
   • Continue for up to 14 days

   Option B: Midodrine plus octreotide plus albumin:

   • Midodrine: Titrate up to maximum 12.5 mg orally three times daily
   • Octreotide: Target dose 200 μg subcutaneously three times daily
   • Albumin: 10-20 g IV daily for up to 20 days
   • Goal: Increase mean arterial pressure by 15 mmHg 1

3. Norepinephrine plus albumin (alternative in ICU setting):

   • Has shown 83% success rate in reversing Type 1 HRS
   • Requires ICU monitoring 1

Definitive Treatment:

Liver transplantation:

• Should be expedited, especially for patients with Type 1 HRS
• Represents the only definitive treatment with long-term survival benefit 1

Bridging Therapies:

1. Renal replacement therapy:

   • Not recommended as first-line therapy
   • May be used to control azotemia and maintain electrolyte balance before liver transplantation
   • Challenges include hypotension during dialysis
   • Continuous venovenous hemofiltration/hemodialysis causes less hypotension but requires continuous nursing care 1, 3

2. Transjugular intrahepatic portosystemic shunt (TIPS):

   • Limited evidence but may improve renal function and natriuresis
   • Consider in selected patients as a bridge to transplantation 1, 4

Treatment Efficacy and Considerations

• Recovery of renal function occurs in less than 50% of patients treated with vasoactive drugs 5
• Without liver transplantation, survival remains poor despite pharmacological treatment
• Patients with serum creatinine >5 mg/dL are unlikely to benefit from terlipressin 2
• Recurrence of HRS after initial treatment may respond to long-term therapy with terlipressin and albumin as a bridge to liver transplantation 5

Monitoring During Treatment

• Urine output
• Fluid balance
• Arterial pressure
• Central venous pressure (ideally)
• Serum creatinine
• Electrolytes
• Signs of potential ischemic events (with vasoconstrictor therapy) 1, 2

Prevention of HRS

• Intravenous albumin infusion in patients with spontaneous bacterial peritonitis
• Oral pentoxifylline in patients with acute alcoholic hepatitis 4

Common Pitfalls

1. Failing to exclude other causes of renal failure before diagnosing HRS:

   • Hypovolemia
   • Shock
   • Parenchymal renal diseases
   • Nephrotoxic drugs

2. Delaying referral for liver transplantation, which remains the only definitive treatment

3. Using renal replacement therapy as first-line treatment rather than vasoactive drugs with albumin

4. Failing to monitor for potential complications of vasoconstrictor therapy, including ischemic events

5. Not recognizing the importance of treating precipitating factors, particularly bacterial infections which are present in approximately 30% of HRS cases 1