What are the types and management of Hepatorenal Syndrome (HRS), including HRS-AKI (Acute Kidney Injury) and HRS-CKD (Chronic Kidney Disease)?

Types and Management of Hepatorenal Syndrome (HRS)

Hepatorenal syndrome (HRS) is classified into four distinct types based on the current international guidelines: HRS-AKI, HRS-AKD, HRS-CKD, and HRS-NAKI, with specific diagnostic criteria and management approaches for each type. 1

Types of Hepatorenal Syndrome

1. HRS-AKI (formerly Type 1 HRS)

• Definition: Acute kidney injury in cirrhosis characterized by:
  • Increase in serum creatinine ≥0.3 mg/dL within 48 hours OR
  • Increase in serum creatinine ≥50% from baseline within 7 days 1, 2
• Clinical features: Rapid, progressive decline in renal function
• Prognosis: Poor, with median survival of approximately 1 month without treatment 1

2. HRS-AKD (Acute Kidney Disease)

• Definition: Estimated GFR <60 mL/min/1.73 m² for <3 months OR
• Increase in serum creatinine ≥50% within 3 months 1
• Clinical features: Less acute than HRS-AKI but not yet chronic

3. HRS-CKD (formerly Type 2 HRS)

• Definition: Estimated GFR <60 mL/min/1.73 m² for ≥3 months 1
• Clinical features: Stable, less severe kidney dysfunction
• Prognosis: Better than HRS-AKI, but still poor overall

4. HRS-NAKI (Non-AKI HRS)

• Definition: Functional kidney injury for >7 days in cirrhosis without meeting AKI criteria 1
• Clinical features: Gradual increase in serum creatinine to >1.5 mg/dL

Diagnostic Criteria for HRS-AKI

1. Cirrhosis with ascites
2. Diagnosis of AKI according to ICA-AKI criteria
3. No response after 2 consecutive days of diuretic withdrawal and plasma volume expansion with albumin (1 g/kg body weight, maximum 100 g/day)
4. Absence of shock
5. No current or recent use of nephrotoxic drugs
6. 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

Management Algorithm for HRS

Step 1: Prevention

• Avoid alcohol use
• Monitor serum creatinine and electrolytes in patients on diuretics
• Administer albumin with therapeutic paracentesis
• Provide antibiotic prophylaxis for spontaneous bacterial peritonitis
• Avoid nephrotoxic medications (NSAIDs, ACE inhibitors, ARBs) 1

Step 2: Initial Management of AKI in Cirrhosis

1. Withdraw potential nephrotoxic agents:

   • Discontinue diuretics
   • Stop beta-blockers
   • Discontinue NSAIDs and other nephrotoxic drugs 1

2. Volume expansion:

   • Administer albumin 1 g/kg body weight (maximum 100 g/day) for two consecutive days 1, 2
   • For specific fluid losses:
     • Diarrhea/excessive diuresis: Replace with crystalloids
     • GI bleeding: Transfuse to maintain hemoglobin 7-9 g/dL 1

3. Identify and treat infections (common precipitating factors) 1

Step 3: Specific Treatment for HRS-AKI

If no response to initial management and patient meets HRS-AKI criteria:

1. First-line therapy: Terlipressin plus albumin 2

   • Terlipressin: 0.5-2.0 mg IV every 4-6 hours or continuous infusion of 2-12 mg/24h
   • Albumin: 1 g/kg body weight per day (maximum 100 g/day)
   • Contraindications: Serum creatinine ≥5 mg/dL, oxygen saturation <90% 1
   • Monitor for: Ischemic complications (angina, digital ischemia), pulmonary edema 1

2. Alternative if terlipressin unavailable:

   • Norepinephrine plus albumin: Starting dose 0.5 mg/h, increase every 4 hours by 0.5 mg/h to maximum 3 mg/h 1, 2
   • OR
   • Midodrine plus octreotide with albumin:
     • Midodrine: 7.5 mg initially, titrate to 12.5 mg TID
     • Octreotide: 100 μg initially, titrate to 200 μg SQ TID 1, 2

3. Duration of therapy:

   • Continue until complete response (serum creatinine returns to within 0.3 mg/dL of baseline)
   • Maximum duration: 14 days 2

Step 4: Renal Replacement Therapy (RRT)

RRT should be considered in:

• AKI secondary to acute tubular necrosis
• HRS-AKI in potential liver transplant candidates
• AKI of uncertain etiology on individual basis 1

Step 5: Definitive Treatment

• Liver transplantation: Most effective treatment for HRS-AKI 1, 2
• Consider simultaneous liver-kidney transplantation in selected patients 1

Important Clinical Pearls

1. Early treatment is crucial: Response rates are significantly higher with lower baseline serum creatinine values 2

2. Transjugular intrahepatic portosystemic shunts (TIPS) should not be used specifically for HRS-AKI treatment 1

3. Biomarkers like urinary NGAL may help differentiate HRS from acute tubular necrosis in difficult cases 1

4. Monitor closely for complications:

   • Fluid overload and pulmonary edema with albumin administration
   • Ischemic complications with vasoconstrictors 1, 2

5. Prognosis: HRS-AKI is associated with high mortality (median survival ≤3 months) without treatment 3, 4

By following this structured approach to diagnosis and management, outcomes can be improved in this challenging clinical condition that significantly impacts morbidity, mortality, and quality of life in patients with cirrhosis.