What are the types and treatment approaches for Hepatorenal Syndrome (HRS) Acute Kidney Injury (AKI)?

Hepatorenal Syndrome Acute Kidney Injury (HRS-AKI): Types and Treatment Approaches

Terlipressin plus albumin is the first-line treatment for HRS-AKI, with treatment initiated promptly once diagnosis is established to improve survival and reduce morbidity. 1, 2

Types of HRS-AKI

According to the International Club of Ascites (ICA) revised classification, HRS is now categorized as:

1. HRS-AKI (formerly Type 1 HRS):

   • Defined as an increase in serum creatinine ≥0.3 mg/dL within 48 hours OR
   • Increase in serum creatinine ≥1.5 times (>50%) from baseline within 7 days 1, 2
   • Characterized by rapid progression of renal failure

2. HRS-NAKI (Non-AKI, formerly Type 2 HRS):

   • Further subdivided into:
     • HRS-AKD (Acute Kidney Disease): eGFR <60 mL/min/1.73 m² for <3 months
     • HRS-CKD (Chronic Kidney Disease): eGFR <60 mL/min/1.73 m² for ≥3 months 1
   • Associated with refractory ascites and slower progression

Diagnostic Criteria for HRS-AKI

All of the following must be present:

• Diagnosis of cirrhosis with ascites
• AKI according to ICA-AKI criteria
• No response after 2 consecutive days of diuretic withdrawal and plasma volume expansion with albumin (1 g/kg body weight, maximum 100 g/day)
• Absence of shock
• No current/recent use of nephrotoxic drugs (NSAIDs, aminoglycosides, contrast media)
• No macroscopic signs of structural kidney injury:
  • Absence of proteinuria (>500 mg/day)
  • Absence of microhematuria (>50 RBCs per high power field)
  • Normal findings on renal ultrasonography 1

Treatment Algorithm for HRS-AKI

Step 1: Initial Management

• Withdraw diuretics and nephrotoxic drugs
• Volume expansion with albumin 1 g/kg/day (maximum 100 g) for 2 consecutive days 1, 2
• Treat precipitating factors (infections, bleeding, etc.)

Step 2: Vasoconstrictor Therapy (if no response to Step 1)

• First-line: Terlipressin plus albumin 1, 2, 3

  • Terlipressin administration options:
    • IV bolus: 1 mg every 4-6 hours, OR
    • Continuous infusion: 2 mg/day
  • Increase dose if serum creatinine doesn't decrease by ≥25% after 2-3 days
  • Maximum dose: 12 mg/day
  • Continue albumin 20-40 g/day during treatment 1, 2

• Alternative if terlipressin unavailable: Norepinephrine plus albumin 1, 2

  • Continuous IV infusion starting at 0.5 mg/h
  • Increase every 4 hours by 0.5 mg/h to maximum 3 mg/h
  • Goal: Increase mean arterial pressure by ≥10 mmHg and/or urine output >50 mL/h

• Less effective alternative: Midodrine plus octreotide with albumin 1, 2

  • Midodrine: 7.5-12.5 mg orally three times daily
  • Octreotide: 100-200 μg subcutaneously three times daily

Step 3: Response Assessment

• 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 1, 2
• Continue treatment until complete response or maximum 14 days 1, 2

Step 4: Definitive Management

• Liver transplantation: Most effective definitive treatment for HRS-AKI 1, 2
• Renal replacement therapy (RRT) indications:
  • AKI secondary to acute tubular necrosis
  • HRS-AKI in potential liver transplant candidates
  • Severe electrolyte/acid-base disturbances or volume overload 1

Important Clinical Considerations

1. Early treatment improves outcomes: Higher pretreatment serum creatinine is associated with treatment failure, so prompt diagnosis and intervention are critical 1, 2

2. Monitoring during treatment:

   • Cardiovascular parameters (blood pressure, heart rate)
   • Signs of ischemic complications (abdominal pain, extremity ischemia)
   • Fluid status to prevent pulmonary edema (occurs in up to 43% of patients) 1, 2

3. Contraindications to terlipressin:

   • Serum creatinine ≥5 mg/dL
   • Oxygen saturation <90%
   • Severe cardiovascular disease 3

4. Response rates:

   • Terlipressin plus albumin: 36-44% complete response 1, 3
   • Higher success rates with earlier treatment initiation 1

5. TIPS (Transjugular Intrahepatic Portosystemic Shunt):

   • Not recommended as specific treatment for HRS-AKI 1
   • May be considered for HRS-NAKI with refractory ascites 1

Pitfalls to Avoid

1. Delaying treatment: Do not wait for serum creatinine to reach a specific threshold before initiating vasoconstrictors in patients meeting HRS-AKI criteria 1

2. Inadequate volume expansion: Ensure proper albumin administration (1 g/kg/day, maximum 100 g) for 2 days before confirming HRS-AKI diagnosis 1

3. Missing precipitating factors: Always identify and treat underlying causes (infections, bleeding, nephrotoxic drugs) 1

4. Overlooking fluid overload: Monitor closely for pulmonary edema during albumin administration, especially in patients with cardiac dysfunction 1, 2

5. Continuing treatment despite ischemic complications: Monitor for and promptly address ischemic side effects of vasoconstrictors 1, 2