What are the types of hepatorenal syndrome (HRS)?

Types of Hepatorenal Syndrome (HRS)

Hepatorenal syndrome is classified into two main types: HRS-AKI (formerly Type 1), which is characterized by rapid, progressive renal failure, and HRS-CKD (formerly Type 2), which presents as a more stable, chronic kidney dysfunction typically associated with refractory ascites. 1

Current Classification of HRS Types

HRS-AKI (Acute Form, formerly Type 1)

• Characterized by rapid deterioration of renal function with a sudden onset of acute kidney injury 2, 1
• Defined according to ICA-AKI criteria with the following stages 2:
  • Stage 1: Increase of creatinine ≥0.3 mg/dL up to 2-fold of baseline
  • Stage 2: Increase in creatinine between 2-fold and 3-fold of baseline
  • Stage 3: Increase in creatinine >3-fold of baseline or creatinine >4 mg/dL with acute increase ≥0.3 mg/dL or initiation of RRT
• Very poor prognosis with median survival of approximately 1-2 weeks if untreated 3, 4
• Often precipitated by bacterial infections, particularly spontaneous bacterial peritonitis (SBP) 2
• Frequently accompanied by rapid deterioration of other organ functions 5

HRS-CKD (Chronic Form, formerly Type 2)

• Presents as a more stable, chronic kidney dysfunction 1
• Characterized by slow and progressive worsening of renal function 5
• Main clinical manifestation is refractory ascites 3, 5
• Better prognosis than HRS-AKI with median survival of approximately 6 months 3, 4

Diagnostic Criteria for HRS

Both types of HRS share common diagnostic criteria:

• Elevated serum creatinine (>133 μmol/L or 1.5 mg/dL) 2
• Absence of other causes of renal failure:
  • Hypovolemia
  • Shock
  • Parenchymal renal diseases
  • Nephrotoxic drugs 2
• Absence of kidney pathology markers:
  • No hematuria
  • No significant proteinuria
  • Normal kidney ultrasonography 6
• Diagnosis requires exclusion of other causes through:
  • Diagnostic paracentesis with SAAG calculation
  • Abdominal and renal ultrasound with Doppler 2

Pathophysiology

HRS develops through four main mechanisms:

1. Splanchnic vasodilation
2. Activation of sympathetic nervous system and renin-angiotensin-aldosterone system
3. Altered cardiac function
4. Increased synthesis of vasoactive mediators 2

Systemic inflammation plays a critical role, with bacterial infections being the most important precipitating factors 2.

Clinical Implications and Management

Treatment Approaches

• Liver transplantation is the only definitive treatment for both types of HRS 2, 5
• Bridge therapies include:
  • Terlipressin plus albumin (first-line for HRS-AKI) 2, 3
  • Norepinephrine plus albumin (in ICU setting) 2
  • Midodrine + octreotide + albumin 2
  • Renal replacement therapy as bridge to transplantation 2
  • Transjugular Intrahepatic Portosystemic Shunt (TIPS) in selected patients 2, 4

Prognosis

• Recovery of renal function occurs in less than 50% of patients with HRS after terlipressin treatment 3
• Untreated HRS-AKI has extremely poor outcomes with median survival of approximately 1 month 2
• Early diagnosis and treatment are critical for improving outcomes 2
• Baseline serum creatinine is a predictor of response to treatment and survival 2

Prevention

• Treatment of spontaneous bacterial peritonitis with albumin plus antibiotics reduces the risk of HRS development 2
• Early recognition and management of precipitating factors is essential