Can diuretics be used in patients with type 1 Hepatorenal Syndrome (HRS) and a history of advanced liver disease?

Diuretics in Hepatorenal Syndrome Type 1: Contraindicated

Diuretics are contraindicated in patients with Type 1 Hepatorenal Syndrome (HRS-1) and should be withdrawn immediately upon diagnosis. 1, 2

Why Diuretics Must Be Stopped in HRS-1

The pathophysiology of HRS-1 involves severe renal vasoconstriction and effective arterial volume depletion despite total body fluid overload. 1 Diuretics worsen this condition by:

• Further depleting effective circulating volume, which exacerbates the already compromised renal perfusion in HRS-1 1
• Accelerating the progression of renal failure in a condition already characterized by rapidly progressive kidney injury (doubling of creatinine to ≥2.5 mg/dL within 2 weeks) 1
• Interfering with the diagnostic workup, as HRS-1 diagnosis requires excluding intravascular volume depletion through diuretic withdrawal and volume expansion 1, 2

The Correct Diagnostic and Treatment Approach

Step 1: Immediate Diuretic Withdrawal

• All diuretics must be discontinued as the first step when HRS-1 is suspected 1, 2
• This withdrawal is mandatory before confirming the diagnosis, as patients must demonstrate lack of sustained improvement in renal function (SCr remaining ≥2.25 mg/dL) 48 hours after diuretic cessation 2

Step 2: Volume Expansion with Albumin

• Administer albumin 1 g/kg on day 1 (maximum 100 g), followed by 20-40 g/day thereafter 1, 2
• This plasma volume expansion is essential to exclude volume-responsive causes of renal failure 1
• The goal is to achieve a central venous pressure of 3 cm of water 1

Step 3: Vasoconstrictor Therapy

• Terlipressin plus albumin is the evidence-based treatment for HRS-1, achieving verified HRS reversal in 29.1% of patients versus 15.8% with albumin alone (p=0.012) 2, 3
• Start terlipressin 0.85 mg IV every 6 hours, increasing to 1.7 mg every 6 hours on day 4 if creatinine decreases by less than 30% 2
• Alternative regimens include octreotide (200 mcg subcutaneously three times daily) plus midodrine (up to 12.5 mg orally three times daily) plus albumin, though this is less effective than terlipressin 1

Critical Clinical Pitfall

The most dangerous error is continuing diuretics in HRS-1 based on the presence of ascites or edema. 1 While these patients have total body sodium and water overload, their effective arterial blood volume is severely depleted. Treating the visible fluid overload with diuretics paradoxically worsens renal perfusion and accelerates progression to irreversible renal failure. 1

When Diuretics May Be Considered (Post-Recovery Only)

• Only after HRS reversal is achieved (two consecutive SCr values ≤1.5 mg/dL at least 2 hours apart) can diuretics be cautiously reintroduced if fluid retention recurs 2
• In the CONFIRM trial, 26% of terlipressin-treated patients received concomitant diuretics, but this was after initial diuretic withdrawal and during recovery phase 2
• Type 2 HRS (more indolent course without rapidly progressive renal failure) may tolerate cautious diuretic use, but this is a fundamentally different clinical entity than Type 1 1

Monitoring During Treatment

• Track serum creatinine every 1-2 days to assess response to vasoconstrictor therapy 2, 3
• Continue albumin throughout treatment course (median dose 50 g/day in clinical trials) 2
• If creatinine remains at or above baseline on day 4 of terlipressin, discontinue therapy as treatment has failed 2
• Terlipressin reduces need for renal replacement therapy by day 30 (28.1% vs 35.9% with placebo, p=0.040) 4

Bridge to Definitive Therapy

• Liver transplantation remains the only definitive cure for HRS-1 5, 6
• Vasoconstrictor therapy serves as a bridge to transplantation, with successful transplantation reported after 34-111 days of terlipressin treatment 5
• Among transplant recipients treated with terlipressin, 60.0% were alive and RRT-free at day 90 versus 39.7% with placebo (p=0.010) 4