Hepatorenal syndrome (HRS)

Diagnosis of HRS-AKI

1. Establish AKI in cirrhosis

• Increase in serum creatinine (SCr) ≥0.3 mg/dL within 48 hours, or
• Increase in SCr ≥50% from baseline within 7 days, and/or
• Urine output ≤0.5 mL/kg/hour for at least 6 hours.

2. Apply current ICA-ADQI HRS-AKI criteria

1. Cirrhosis with ascites
2. AKI meeting the criteria above
3. No improvement in creatinine and/or urine output within 24 hours after appropriate volume resuscitation, when volume depletion is present
4. No strong alternative cause as the main explanation for AKI.

3. Assess volume status and exclude/treat alternative causes

Older exam-style criteria

Management of HRS-AKI

Immediate measures

1. Admit and monitor closely
   • Strict input-output chart, daily weight, frequent SCr, electrolytes, blood pressure/MAP, oxygen saturation.
   • Consider ICU if hypotension, septic shock, respiratory compromise, or vasopressor requirement.
2. Find and correct the precipitant
   • Infection, especially SBP
   • GI bleeding
   • Overdiuresis or diarrhea/vomiting
   • Large-volume paracentesis without albumin
   • Alcohol-associated hepatitis or acute hepatic decompensation
   • Nephrotoxic medication exposure
3. Stop aggravating drugs
   • Stop diuretics initially.
   • Withhold NSAIDs, ACE inhibitors/ARBs, and other nephrotoxins.
   • Avoid unnecessary contrast.
4. Restore effective arterial volume appropriately
   • If clinically volume depleted, give resuscitation promptly.
   • Albumin is particularly useful when SBP or post-paracentesis circulatory dysfunction is present.
   • Do not give albumin indiscriminately in pulmonary edema or fluid overload.

Specific therapy: vasoconstrictor plus albumin

First choice: terlipressin + 20-25% albumin

• Terlipressin is the preferred vasoconstrictor where available.
• Albumin is given alongside it, commonly 20-40 g/day, then adjusted daily to volume status.
• Escalate terlipressin according to local protocol if creatinine has not fallen adequately.
• Assess for renal response using SCr and urine output.

• Continuous or frequent oxygen saturation assessment.
• Watch for pulmonary edema/fluid overload, ischemia, abdominal pain, diarrhea, arrhythmia, and respiratory deterioration.
• Avoid or withhold terlipressin in significant hypoxia, worsening respiratory symptoms, or ongoing coronary, peripheral, or mesenteric ischemia. Terlipressin safety guidance

Alternative: norepinephrine + albumin

• Appropriate when terlipressin is unavailable or unsuitable.
• Usually requires an ICU or closely monitored setting, often with central venous access.
• Titrate to increase MAP, commonly targeting a rise of about 10 mmHg or more from baseline.

Third-line option: midodrine + octreotide + albumin

• Use only when terlipressin and norepinephrine cannot be used.
• It is less effective than terlipressin or norepinephrine.
• Typical approach is oral midodrine titrated to raise MAP, plus subcutaneous octreotide and IV albumin, following local specialist protocol.

When to stop vasoconstrictor treatment

• Response: SCr returns to within 0.3 mg/dL of baseline
• No meaningful renal improvement despite adequate treatment, often assessed after several days
• Dialysis becomes necessary or there is persistent anuria/non-response
• Serious adverse effect, especially ischemia, hypoxia, or respiratory failure
• Maximum treatment duration is reached, commonly up to 14 days

Renal replacement therapy

• Refractory hyperkalemia
• Severe metabolic acidosis
• Pulmonary edema/volume overload refractory to therapy
• Uremic complications
• Severe persistent AKI as a bridge to transplantation or recovery from a reversible insult

Definitive treatment

Liver transplantation

Practical one-line algorithm

FDA-labeled IV bolus regimen

• Days 1-3: 0.85 mg IV over 2 minutes every 6 hours
  • Equivalent to 1 mg terlipressin acetate every 6 hours.
• Day 4: assess serum creatinine relative to pretreatment baseline:
  • SCr decreased ≥30%: continue 0.85 mg IV every 6 hours
  • SCr decreased <30%: increase to 1.7 mg IV every 6 hours
    • Equivalent to 2 mg terlipressin acetate every 6 hours
  • SCr at or above baseline: discontinue treatment.
• Continue until 24 hours after the second consecutive SCr value ≤1.5 mg/dL at least 2 hours apart, or for a maximum 14 days.

Albumin co-therapy

• Common regimen: 1 g/kg IV on day 1 (maximum 100 g), then 20-40 g/day thereafter, adjusted to intravascular volume status.
• Stop or reduce albumin with pulmonary edema or volume overload.

Alternative continuous-infusion regimen

• Start 2 mg/day by continuous IV infusion
• Increase every 24-48 hours as needed, up to 12 mg/day, until creatinine improves.

Safety monitoring