What is the initial treatment for Hepato-Renal Syndrome (HRS)?

Initial Treatment for Hepatorenal Syndrome (HRS)

The initial treatment of choice for Hepatorenal Syndrome is vasoconstrictor therapy with terlipressin plus albumin infusion. 1

Diagnostic Confirmation

Before initiating treatment, confirm HRS diagnosis with these criteria:

• Cirrhosis with ascites
• Acute kidney injury (AKI) according to International Club of Ascites criteria
• No response after diuretic withdrawal and volume expansion
• Absence of shock
• No recent use of nephrotoxic drugs
• No signs of structural kidney injury

First-Line Treatment Protocol

Step 1: Initial Volume Expansion

• Withdraw all diuretics
• Administer albumin at 1 g/kg body weight (maximum 100 g/day) for two consecutive days 2
• Assess response by measuring serum creatinine daily

Step 2: Vasoconstrictor Therapy

If no improvement after albumin administration, initiate vasoconstrictor therapy:

First Choice: Terlipressin + Albumin 1, 2

• Terlipressin: 0.5-2.0 mg IV every 4-6 hours or continuous IV infusion of 2-12 mg/24h
• Albumin: 20-40 g/day IV

If Terlipressin Unavailable: Alternative Options (in order of preference)

1. Norepinephrine + Albumin 1

   • Norepinephrine: 0.5-3.0 mg/h continuous IV infusion
   • Albumin: 20-40 g/day IV

2. Midodrine + Octreotide + Albumin 1

   • Midodrine: 7.5-12.5 mg orally three times daily
   • Octreotide: 100-200 μg subcutaneously three times daily
   • Albumin: 20-40 g/day IV

Evidence-Based Rationale

Terlipressin plus albumin is the most effective treatment, with response rates of 29.1% versus 15.8% with placebo in the CONFIRM trial 3. Multiple guidelines consistently recommend this combination as first-line therapy 1, 2.

Comparative efficacy data shows:

• Terlipressin + albumin achieves renal function recovery in 70.4% of patients versus 28.6% with midodrine/octreotide + albumin 4
• Norepinephrine + albumin achieves full response in 57.6% of patients versus 20% with midodrine/octreotide + albumin 5

Treatment Duration and Response Assessment

• Continue treatment for up to 14 days
• Complete response: return of serum creatinine to within 0.3 mg/dL of baseline
• Partial response: regression of AKI stage with serum creatinine ≥0.3 mg/dL above baseline
• If no response after 4 days with maximum tolerated doses, consider discontinuing therapy 1

Monitoring During Treatment

• Daily serum creatinine
• Cardiovascular parameters (blood pressure, heart rate)
• Signs of volume overload or pulmonary edema
• Ischemic complications (abdominal pain, digital ischemia)

Important Considerations

• Early initiation is crucial - response rates are higher with lower baseline serum creatinine 2
• Contraindications to terlipressin: serum creatinine ≥5 mg/dL, oxygen saturation <90%, severe cardiovascular disease 2
• Liver transplantation remains the definitive treatment for HRS 6
• Renal replacement therapy should be considered for patients awaiting liver transplantation who have worsening renal function, electrolyte disturbances, or increasing volume overload unresponsive to vasoconstrictor therapy 1

Common Pitfalls to Avoid

1. Delaying treatment initiation - early intervention is associated with better outcomes
2. Inadequate albumin dosing - underdosing reduces efficacy
3. Failing to monitor for adverse effects of vasoconstrictors (ischemic complications)
4. Not considering liver transplantation evaluation promptly
5. Continuing ineffective therapy beyond 4 days if no response is observed

The evidence clearly demonstrates that vasoconstrictor therapy with terlipressin plus albumin offers the best chance for reversing HRS and improving survival, with norepinephrine as a reasonable alternative when terlipressin is unavailable.