Types of Hepatorenal Syndrome
Hepatorenal syndrome (HRS) is currently classified into two main types: HRS-AKI (formerly Type 1 HRS) and HRS-NAKI (formerly Type 2 HRS), with the classification having evolved from the traditional Type 1 and Type 2 designations to better align with modern acute kidney injury criteria. 1, 2
Current Classification of Hepatorenal Syndrome
HRS-AKI (formerly Type 1 HRS)
- Characterized by rapid deterioration of renal function
- Defined by AKI stage 2 or higher according to KDIGO criteria:
- Increase in serum creatinine 2-3 times baseline
- Increase to >4 mg/dL with an acute increase of ≥0.3 mg/dL
- Initiation of renal replacement therapy 1
- Often precipitated by infections (particularly spontaneous bacterial peritonitis), acute alcoholic hepatitis, or other acute events 1, 3
- Associated with very poor prognosis (median survival approximately 2 weeks without treatment) 4
- Main clinical presentation is rapidly progressive renal failure 2
HRS-NAKI (formerly Type 2 HRS)
- Characterized by more stable or slowly progressive renal dysfunction 1, 5
- Develops over weeks to months 5
- Better prognosis than HRS-AKI (median survival approximately 6 months) 4
- Main clinical manifestation is refractory ascites 4, 3
Diagnostic Criteria for Hepatorenal Syndrome
According to the American Association for the Study of Liver Diseases (AASLD), HRS diagnosis requires:
- Presence of cirrhosis with ascites
- Acute kidney injury (AKI) stage 2 or higher
- No response to diuretic withdrawal and volume expansion with albumin
- Absence of shock, nephrotoxicity, or structural kidney disease
- No proteinuria, hematuria, and normal renal ultrasound 1
Pathophysiology
HRS develops through four main mechanisms:
- Splanchnic vasodilation
- Activation of sympathetic nervous system and renin-angiotensin-aldosterone system
- Altered cardiac function
- Increased synthesis of vasoactive mediators 1
It's important to note that recent evidence suggests HRS is not purely "functional" as traditionally thought, but also involves systemic inflammation, oxidative stress, and bile salt-related tubular damage, which may explain why some patients don't respond to vasoconstrictor therapy 2.
Treatment Approach
First-line treatment for HRS-AKI:
- Terlipressin plus albumin
- Initial dose: 1 mg IV every 4-6 hours
- Can be increased to 2 mg every 4-6 hours if serum creatinine decreases <25% after 2 days
- Maximum dose: 12 mg/day
- Albumin: 1.5 g/kg on day 1, followed by 1 g/kg on day 3 1
Alternative treatments:
- Norepinephrine plus albumin (when terlipressin unavailable)
- Dose: 0.5-3 mg/hour as continuous infusion
- Requires ICU setting and central venous access 1
- Midodrine + octreotide + albumin
- Midodrine: titrated up to 12.5 mg orally three times daily
- Octreotide: 200 μg subcutaneously three times daily
- Albumin: 10-20 g/day IV for up to 20 days 1
Definitive treatment:
Important Clinical Considerations
- Early diagnosis and treatment are critical for improving outcomes 1
- Higher baseline serum creatinine predicts poorer response to vasoconstrictors 1
- Recovery of renal function occurs in less than 50% of patients with HRS after terlipressin treatment 4
- HRS-AKI can evolve into acute tubular necrosis if left untreated 5
- Renal replacement therapy should not be considered first-line therapy but may be used as a bridge to liver transplantation 1, 4
Common Pitfalls in HRS Management
- Delayed diagnosis: HRS is a diagnosis of exclusion, requiring thorough evaluation to rule out other causes of AKI in cirrhosis
- Inadequate volume expansion: Failure to provide adequate albumin during treatment reduces efficacy
- Failure to recognize and treat precipitating factors: Especially bacterial infections
- Delayed referral for liver transplantation: This remains the definitive treatment
- Overlooking the possibility of HRS progression: HRS-NAKI can progress to HRS-AKI, particularly with precipitating events 1, 5