What are the different types of hepatorenal syndrome (HRS)?

Types of Hepatorenal Syndrome

Hepatorenal syndrome (HRS) is classified into two distinct types: Type 1 HRS, characterized by rapid and progressive impairment in renal function, and Type 2 HRS, characterized by stable or less progressive impairment in renal function. 1

Type 1 HRS (HRS-AKI)

Type 1 HRS is defined by the following characteristics:

• Rapid and progressive deterioration of renal function 1
• Increase in serum creatinine of equal to or greater than 100% compared to baseline 1
• Serum creatinine level rising to higher than 2.5 mg/dl 1
• Development occurs in less than 2 weeks 1, 2
• Often precipitated by a triggering event, particularly bacterial infections (especially spontaneous bacterial peritonitis) 1, 3
• Associated with very poor prognosis - median survival of approximately 1 month if untreated 1, 4
• Main clinical presentation is acute kidney failure 5

Type 2 HRS

Type 2 HRS is characterized by:

• Stable or slowly progressive impairment in renal function 1
• More chronic course compared to Type 1 HRS 2, 6
• Better survival compared to Type 1 HRS (median survival approximately 6 months) 4
• Main clinical manifestation is refractory ascites 4, 5
• May occur without an obvious precipitating event 5

Diagnostic Criteria for HRS

For both types of HRS, diagnosis requires meeting the following criteria:

• Serum creatinine >1.5 mg/dl (133 μmol/L) 1, 2
• Absence of shock 1
• No improvement of renal function (creatinine decreasing to <133 μmol/L) after at least 2 days of:
  • Diuretic withdrawal (if on diuretics) 1
  • Volume expansion with albumin (1 g/kg/day up to maximum 100 g/day) 1
• No current or recent treatment with nephrotoxic drugs 1
• Absence of parenchymal renal disease as defined by:
  • Proteinuria <0.5 g/day 1
  • No microhematuria (<50 red cells/high powered field) 1
  • Normal renal ultrasonography 1

Pathophysiology

Four main factors are involved in the pathogenesis of HRS:

1. Splanchnic vasodilation causing reduction in effective arterial blood volume and decreased mean arterial pressure 1
2. Activation of sympathetic nervous system and renin-angiotensin-aldosterone system causing renal vasoconstriction 1
3. Impairment of cardiac function due to cirrhotic cardiomyopathy 1
4. Increased synthesis of vasoactive mediators affecting renal blood flow 1
5. Systemic inflammation, oxidative stress, and bile salt-related tubular damage (newer understanding) 5

Risk Factors and Prognosis

• Bacterial infections, particularly spontaneous bacterial peritonitis (SBP), are the most important risk factors for HRS 1, 7
• HRS develops in approximately 30% of patients with SBP 1
• Overall prognosis is poor, with average median survival of approximately 3 months 1
• Type 1 HRS has worse prognosis than Type 2 HRS 1, 4
• High MELD scores are associated with very poor prognosis 1

Recent Developments in Classification

Recent literature has proposed updating the nomenclature:

• Type 1 HRS is now often referred to as HRS-AKI (Acute Kidney Injury) 2, 5
• This reflects the adoption of acute kidney injury staging criteria from nephrology 5
• The understanding of HRS has evolved from a purely "functional" entity to one that may also involve structural components 5

Treatment Considerations

• Liver transplantation is the definitive treatment for both types of HRS 7, 2
• Vasoconstrictors (particularly terlipressin) plus albumin are the first-line pharmacological therapy for Type 1 HRS 7, 2, 4
• Recovery of renal function can be achieved in less than 50% of patients with HRS after terlipressin use 4
• Patients with Type 1 HRS should be monitored carefully in intensive or semi-intensive care units 1

Understanding the differences between these two types of HRS is crucial for appropriate management and prognostication in patients with advanced liver disease.