What is the current management of Hepatorenal Syndrome (HRS) Acute Kidney Injury (AKI)?

Current Management of Hepatorenal Syndrome Acute Kidney Injury (HRS-AKI)

Terlipressin plus albumin is the first-line treatment for HRS-AKI, with norepinephrine as an alternative when terlipressin is unavailable or contraindicated. 1

Diagnosis and Initial Management

Diagnostic Criteria for HRS-AKI

• 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
• Presence of cirrhosis with ascites
• No response to diuretic withdrawal and 2-day volume challenge with albumin
• No shock, recent nephrotoxic drugs, or signs of structural kidney damage 1, 2

Initial Steps

1. Withdraw diuretics and treat precipitating factors (bacterial infections, GI bleeding)
2. Volume expansion with albumin 1 g/kg body weight per day (maximum 100 g/day) for 2 consecutive days 1
3. Reassess renal function after 48 hours of albumin challenge

Pharmacological Treatment

First-Line Therapy: Terlipressin + Albumin

• Terlipressin administration options:

  • Bolus dosing: Start at 1 mg every 4-6 hours IV
  • Continuous infusion: Start at 2 mg/day (may reduce side effects)
  • Increase dose if no reduction in serum creatinine by ≥25% after 2-3 days
  • Maximum dose: 12 mg/day
  • Continue for up to 14 days or until serum creatinine returns to within ≤0.3 mg/dL of baseline for 2 consecutive days 1

• Albumin maintenance: 20-40 g/day during vasoconstrictor treatment 1, 2

• FDA restrictions: Avoid terlipressin if serum creatinine ≥5 mg/dL or oxygen saturation <90% 1, 3

Alternative Vasoconstrictors

• Norepinephrine: 0.5 mg/h continuous IV infusion, increased 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 to >50 mL/h for at least 4 hours
  • Requires central venous line and often ICU admission 1

• Midodrine + Octreotide (if terlipressin and norepinephrine unavailable):

  • Midodrine: Start at 7.5 mg orally TID, titrate up to 12.5 mg TID
  • Octreotide: Start at 100 μg SC TID, titrate up to 200 μg TID
  • Less effective than terlipressin or norepinephrine 1, 2

Monitoring and Side Effect Management

Close Monitoring Required

• Cardiovascular: ECG, blood pressure, heart rate
• Respiratory: Oxygen saturation, signs of pulmonary edema
• Peripheral circulation: Check for digital ischemia
• Fluid status: Avoid volume overload with excessive albumin 1, 2

Potential Adverse Effects

• Ischemic complications: Angina, arrhythmias, digital/splanchnic ischemia
• Respiratory: Pulmonary edema (especially with terlipressin + albumin)
• Gastrointestinal: Abdominal pain, diarrhea 1, 3

Management of Side Effects

• Start at lowest dose and gradually titrate up to minimize ischemic complications
• Discontinue treatment if severe side effects occur
• Modify albumin dosing if signs of volume overload develop 1

Response Assessment and Further Management

Response Criteria

• Complete response: Final serum creatinine within 0.3 mg/dL from baseline
• Partial response: Regression of AKI stage with final serum creatinine ≥0.3 mg/dL from baseline 1

Management Based on Response

• Response achieved: Continue treatment until serum creatinine stabilizes
• No response after dose escalation: Consider renal replacement therapy (RRT) if liver transplant candidate
• Recurrence after treatment: Repeat course of therapy 1

Definitive Treatment and Special Considerations

Liver Transplantation

• Most effective definitive treatment for HRS-AKI
• Pharmacotherapy before transplantation may improve post-transplant outcomes
• Selected patients may require simultaneous liver-kidney transplantation 1

Renal Replacement Therapy

• Indications:
  • AKI secondary to acute tubular necrosis
  • HRS-AKI in potential liver transplant candidates
  • AKI of uncertain etiology (individualized decision)
  • Severe electrolyte/acid-base disturbances or volume overload 1

TIPS (Transjugular Intrahepatic Portosystemic Shunt)

• Not recommended as specific treatment for HRS-AKI
• Limited applicability due to contraindications in severe liver failure 1
• Currently being investigated in clinical trials 4

Important Caveats

• Response rates to terlipressin plus albumin range from 36-44% 1, 5
• Higher pretreatment serum creatinine is associated with treatment failure 1
• Even small reductions in serum creatinine are beneficial; every 1 mg/dL drop is associated with 27% reduction in mortality risk 1
• Patients with advanced liver disease and ACLF-3 have higher risk of respiratory complications with terlipressin 1
• Efficacy decreases significantly in recurrent HRS-AKI 2