What is the management of hepatorenal syndrome?

Management of Hepatorenal Syndrome

Liver transplantation is the definitive treatment for hepatorenal syndrome, while vasoconstrictor therapy with terlipressin plus albumin is the first-line pharmacological treatment for type 1 HRS (HRS-AKI) to bridge patients to transplantation or treat those who are not transplant candidates. 1

Types of Hepatorenal Syndrome

• Type 1 HRS (HRS-AKI): Characterized by rapidly progressive reduction in renal function with doubling of serum creatinine to >2.5 mg/dL or 50% reduction of 24-hour creatinine clearance to <20 mL/minute within 2 weeks 1
• Type 2 HRS (HRS-CKD): Features a slower, progressive course without rapid deterioration and is commonly associated with refractory ascites 1

Diagnostic Criteria

HRS is diagnosed by excluding other causes of acute kidney injury in cirrhotic patients with:

• Advanced cirrhosis with ascites 1
• Serum creatinine >1.5 mg/dL 1
• No improvement after at least 2 days of diuretic withdrawal and volume expansion with albumin (1 g/kg body weight/day up to 100 g/day) 1
• Absence of shock 1
• No current/recent nephrotoxic drug exposure 1
• Absence of parenchymal kidney disease (proteinuria <500 mg/day, minimal hematuria, normal renal ultrasound) 1

Treatment Algorithm

First-Line Treatment

1. Vasoconstrictor therapy plus albumin:

   • Terlipressin plus albumin is the first-line pharmacological treatment for type 1 HRS 1, 2

     • Initial dose: 1 mg IV every 4-6 hours
     • If serum creatinine doesn't decrease by at least 25% after 3 days, increase dose stepwise to maximum 2 mg every 4 hours
     • Continue until serum creatinine decreases to <1.5 mg/dL (complete response)
     • Discontinue after 14 days if no response or only partial response
     • Monitor for ischemic and respiratory complications

   • Midodrine plus octreotide plus albumin (alternative in regions where terlipressin is unavailable) 1

     • Midodrine: titrated up 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
     • Goal: increase mean arterial pressure by 15 mmHg

   • Norepinephrine plus albumin (requires ICU setting) 1, 3

     • Shown to be effective in 83% of patients with type 1 HRS in pilot studies

2. Liver transplantation: Definitive treatment for both type 1 and type 2 HRS 1, 4

   • Expedited referral for transplantation is recommended for patients with type 1 HRS 1
   • Survival rates approximately 65% in type 1 HRS after transplantation 1
   • Combined liver-kidney transplantation generally not necessary except in patients who have been on prolonged renal support therapy (>12 weeks) 1

Second-Line Treatments

1. Transjugular intrahepatic portosystemic shunt (TIPS) 1

   • May improve renal function in selected patients with type 1 and type 2 HRS
   • Limited applicability due to frequent contraindications in advanced cirrhosis
   • Insufficient data to support routine use as primary treatment

2. Renal replacement therapy 1

   • Useful in patients who don't respond to vasoconstrictors and meet criteria for renal support
   • Options include hemodialysis or continuous venovenous hemofiltration
   • Primarily used as a bridge to liver transplantation
   • Continuous venovenous hemofiltration causes less hypotension but requires continuous nursing care 1

Prevention of HRS

• Norfloxacin (400 mg/day) has been shown to reduce the incidence of HRS in advanced cirrhosis 1
• Pentoxifylline (400 mg three times daily) may prevent HRS development in patients with severe alcoholic hepatitis 1
• Early treatment of bacterial infections and avoidance of nephrotoxic drugs 5, 4

Special Considerations and Pitfalls

• Without liver transplantation, survival is dismal even with temporary improvement in renal function 1
• Patients with serum creatinine >5 mg/dL are unlikely to benefit from terlipressin therapy 2
• Differentiating HRS from acute tubular necrosis can be challenging but is crucial for appropriate management 6, 4
• Response to vasoconstrictors with reduction in serum creatinine is associated with improved survival, though overall survival benefit of vasoconstrictors has not been definitively shown 3
• Treatment with vasoconstrictors before transplantation may improve post-transplant outcomes 1
• Reduction in serum creatinine after treatment should not change the decision to perform liver transplantation since prognosis remains poor 1