What is the management of Hepato-Renal Syndrome (HRS)?

Management of Hepatorenal Syndrome (HRS)

Terlipressin plus albumin is the first-line treatment for hepatorenal syndrome, with terlipressin started at 1 mg every 4-6 hours and increased to a maximum of 2 mg every 4-6 hours if serum creatinine doesn't decrease by at least 25% after 3 days of therapy. 1, 2

Definition and Classification

• HRS is defined as the occurrence of renal failure in patients with advanced liver disease in the absence of identifiable causes of renal failure 1

• Diagnostic criteria include:

  • Serum creatinine >1.5 mg/dL (133 μmol/L)
  • Absence of shock
  • No improvement in renal function after diuretic withdrawal and volume expansion with albumin (1 g/kg/day up to 100 g/day)
  • No current or recent treatment with nephrotoxic drugs
  • Absence of parenchymal renal disease (proteinuria <0.5 g/day, no microhematuria, normal renal ultrasound) 1, 3

• HRS is classified into two types:

  • Type 1 HRS (now termed HRS-AKI): Rapid, progressive impairment in renal function (increase in serum creatinine ≥100% to >2.5 mg/dL in <2 weeks)
  • Type 2 HRS (now termed HRS-NAKI): Stable or less progressive impairment in renal function 1, 2

Pathophysiology

• Four key factors contribute to HRS development:
  1. Splanchnic vasodilation causing reduced effective arterial blood volume and decreased mean arterial pressure
  2. Activation of sympathetic nervous system and renin-angiotensin-aldosterone system causing renal vasoconstriction
  3. Impaired cardiac function due to cirrhotic cardiomyopathy
  4. Increased synthesis of vasoactive mediators affecting renal blood flow 1, 3
• Systemic inflammation plays an important role in HRS pathophysiology 1, 4

Risk Factors and Prognosis

• Bacterial infections, particularly spontaneous bacterial peritonitis (SBP), are the most important risk factors for HRS 1
• HRS develops in approximately 30% of patients who develop SBP 1
• Prognosis is poor:
  • Median survival of all HRS patients: approximately 3 months
  • Median survival of untreated type 1 HRS: approximately 1 month 1, 3
• High MELD scores and type 1 HRS are associated with very poor prognosis 1

Management Approach

General Measures

• Early diagnosis of HRS and exclusion of other causes of renal failure is crucial 1
• Careful monitoring of patients with type 1 HRS:
  • Urine output
  • Fluid balance
  • Arterial pressure
  • Standard vital signs
  • Central venous pressure (ideally) 1
• Patients with type 1 HRS are best managed in intensive care or semi-intensive care units 1

Pharmacological Treatment

1. First-line therapy: Terlipressin plus albumin

   • Terlipressin dosing:
     • Initial dose: 1 mg every 4-6 hours IV bolus over 2 minutes
     • Increase to 2 mg every 4-6 hours if serum creatinine doesn't decrease by at least 25% after 3 days
     • Continue until serum creatinine decreases below 1.5 mg/dL (133 μmol/L) 1, 5
   • Albumin administration: 1 g/kg on first day (maximum 100 g) followed by 20-40 g/day 5, 2
   • Treatment is effective in 40-50% of patients 1, 6
   • Response is characterized by:
     • Progressive reduction in serum creatinine
     • Increase in arterial pressure
     • Increase in urine volume
     • Increase in serum sodium concentration 1
   • Median time to response: 14 days (shorter with lower baseline serum creatinine) 1
   • Predictors of response:
     • Serum bilirubin <10 mg/dL before treatment
     • Increase in mean arterial pressure >5 mmHg at day 3 of treatment 1

2. Alternative therapies (when terlipressin is unavailable):

   • Midodrine plus octreotide plus albumin
   • Norepinephrine plus albumin (requires ICU setting) 2

Liver Transplantation

• Liver transplantation is the definitive treatment for both type 1 and type 2 HRS 2, 6
• Expedited referral is recommended for type 1 HRS 2
• Post-transplant survival rates are approximately 65% 2

Other Treatment Options

• Transjugular intrahepatic portosystemic shunts (TIPS) has shown encouraging results but experience is limited 6
• Extracorporeal albumin dialysis (ECAD) has also shown promising results but with limited experience 6
• Automated low-flow ascites pump (ALFApump) may be considered in special circumstances, but with robust arrangements for clinical governance 1

Prevention of HRS

• Albumin infusion with antibiotics when treating spontaneous bacterial peritonitis 1, 2
• Antibiotic prophylaxis against spontaneous bacterial peritonitis 3
• Avoidance of nephrotoxic medications in patients with advanced cirrhosis 3, 2
• Pentoxifylline may prevent HRS in severe alcoholic hepatitis 2

Monitoring During Treatment

• Monitor for potential adverse effects of terlipressin:
  • Ischemic events (cardiac, intestinal, peripheral)
  • Electrolyte abnormalities 5
• Monitor for fluid overload when administering albumin due to risk of pulmonary edema 3
• Assess serum creatinine regularly to evaluate treatment response 1