How should albumin be dosed and administered with a vasoconstrictor for treating hepatorenal syndrome in a patient with advanced cirrhosis and ascites?

Role of Albumin in Treatment of Hepatorenal Syndrome

Albumin is essential in HRS treatment and must be administered at 1 g/kg (maximum 100 g) on day 1, followed by 20–40 g/day, always in combination with a vasoconstrictor—never as monotherapy. 1, 2

Initial Diagnostic Volume Expansion

Before diagnosing HRS-AKI, you must perform a diagnostic trial of volume expansion to exclude prerenal acute kidney injury:

• Administer albumin 1 g/kg daily for 2 consecutive days (capped at 100 g/day) after withdrawing all diuretics 1
• Albumin is superior to saline for restoring effective arterial blood volume in cirrhosis with ascites 1
• Lack of response to this albumin challenge (failure to improve serum creatinine) is one of the diagnostic criteria for HRS-AKI 1
• This step differentiates HRS-AKI from volume-responsive prerenal azotemia, which accounts for 27–50% of AKI in cirrhosis 2

Treatment Dosing Protocol with Vasoconstrictors

Once HRS-AKI is confirmed, albumin dosing shifts to a maintenance regimen combined with vasoconstrictors:

Day 1 Loading Dose

• Albumin 1 g/kg body weight (maximum 100 g) administered intravenously as 20% or 25% solution 1, 2, 3
• The 100 g cap is critical—higher doses are associated with worse outcomes due to volume overload 3

Maintenance Dosing (Day 2 Onward)

• Albumin 20–40 g/day intravenously, adjusted based on volume status 1, 2
• Continue until complete response (serum creatinine ≤1.5 mg/dL on two occasions ≥2 hours apart) or maximum 14 days 2
• Median time to response is 14 days, shorter in patients with lower baseline creatinine 2

Vasoconstrictor Combinations

Albumin is never used alone for HRS treatment—it must be paired with a vasoconstrictor: 3

• First-line: Terlipressin 1 mg IV every 4–6 hours (equivalent to 0.85 mg terlipressin acetate), escalate to 2 mg every 4 hours if creatinine hasn't decreased ≥25% by day 3–4 1, 2, 4
• Alternative: Norepinephrine 0.5–3 mg/hour continuous IV infusion (requires ICU and central access), titrated to increase MAP by 10–15 mmHg 1, 2
• Third-line: Midodrine/octreotide (when terlipressin unavailable): midodrine 7.5–12.5 mg PO TID plus octreotide 100–200 μg SC TID, with albumin 10–20 g/day for up to 20 days 1, 2, 3

Monitoring and Volume Status Assessment

The 2024 AGA guideline acknowledges a critical gap: the best method to assess volume status is still unknown, yet albumin should ideally be tailored to avoid both under-resuscitation and volume overload 1

Key monitoring parameters:

• Central venous pressure (when available) to guide fluid balance and prevent overload 1, 2
• Watch vigilantly for pulmonary edema, especially in patients with underlying cardiac dysfunction or cirrhotic cardiomyopathy 1, 2
• The ATTIRE trial showed that aggressive albumin dosing (10× higher than controls) increased pulmonary edema rates 1
• Serum creatinine every 2–3 days to assess renal response 2
• Urine output and serum sodium should rise with effective treatment 2

Critical Pitfalls to Avoid

Do not administer fixed albumin doses without considering volume status—routine fixed dosing may cause volume overload and pulmonary edema in some patients or be insufficient in others 1

Do not continue albumin if anasarca develops—discontinue albumin but continue vasoconstrictors 2

Do not use albumin for uncomplicated ascites or after large-volume paracentesis in HRS patients—these are separate indications with different dosing 1

Do not replace albumin with crystalloids or synthetic colloids (hydroxyethyl starch)—these have not been shown to be effective and may cause harm in patients at risk for AKI 3

Evidence Strength and Rationale

The combination of terlipressin plus albumin achieves HRS reversal in 64–76% of patients, significantly superior to albumin alone 2. The CONFIRM trial (FDA approval study) demonstrated 29.1% verified HRS reversal with terlipressin plus albumin versus 15.8% with placebo plus albumin (p=0.012) 4. Each 1 mg/dL reduction in serum creatinine during therapy is associated with a 27% decrease in mortality risk 2.

Albumin provides both volume expansion and anti-inflammatory effects that are mechanistically essential for counteracting the splanchnic vasodilation and effective arterial hypovolemia that characterize HRS pathophysiology 1, 2.