What are the 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 renal impairment with creatinine increasing ≥100% from baseline to >2.5 mg/dL in less than 2 weeks, and type 2 HRS, characterized by stable or slowly progressive renal dysfunction. 1, 2

Diagnostic Criteria for HRS

Before discussing the types in detail, it's important to understand the diagnostic criteria for HRS:

• Serum creatinine >1.5 mg/dL (133 μmol/L) 1
• Absence of shock 1
• No improvement of renal function after:
  • At least 2 days of diuretic withdrawal (if on diuretics) 1, 2
  • 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 evidenced by:
  • Proteinuria <0.5 g/day 1
  • No microhematuria (<50 red cells/high powered field) 1
  • Normal renal ultrasonography 1

Type 1 HRS (HRS-AKI)

• Definition: Rapid and progressive impairment in renal function with serum creatinine increasing ≥100% from baseline to >2.5 mg/dL in less than 2 weeks 1, 2
• Clinical presentation: Acute kidney injury often precipitated by a trigger, commonly bacterial infections (particularly spontaneous bacterial peritonitis) 1, 3
• Prognosis: Very poor with median survival of approximately 1 month if untreated 1, 4
• Mortality: Associated with high MELD scores and extremely poor outcomes 1, 3

Type 2 HRS

• Definition: Stable or less progressive impairment in renal function compared to type 1 HRS 1, 2
• Clinical presentation: More chronic course, often manifesting as refractory ascites 5, 4
• Prognosis: Better survival compared to type 1 HRS, with median survival of approximately 6 months 5, 4

Pathophysiology of HRS

Four key factors contribute to the development of both types of HRS:

1. Splanchnic vasodilation: Causes reduction in effective arterial blood volume and decreased mean arterial pressure 1, 6
2. Activation of sympathetic nervous system and renin-angiotensin-aldosterone system: Results in renal vasoconstriction and altered renal autoregulation 1, 6
3. Impaired cardiac function: Cirrhotic cardiomyopathy leads to inadequate compensatory increase in cardiac output 1
4. Increased synthesis of vasoactive mediators: Including cysteinyl leukotrienes, thromboxane A2, F2-isoprostanes, and endothelin-1 1

Recent Developments in Classification

Recent literature has proposed revising the nomenclature, with type 1 HRS being renamed as HRS-AKI to align with current acute kidney injury definitions used in nephrology 7. This reflects growing recognition that HRS is not purely "functional" but may have structural components related to systemic inflammation, oxidative stress, and bile salt-related tubular damage 7.

Management Considerations

• Type 1 HRS: Requires urgent intervention with vasoconstrictors plus albumin 2, 3

  • First-line: Terlipressin plus albumin 2, 5
  • Alternative options: Midodrine plus octreotide plus albumin, or norepinephrine plus albumin 2, 3

• Type 2 HRS: Management focuses on controlling ascites and maintaining renal function 5

• Definitive treatment: Liver transplantation for both types, with expedited referral recommended for type 1 HRS 2, 3

Common Pitfalls in HRS Management

• Delayed diagnosis: Failing to exclude other causes of renal failure can delay appropriate treatment 1
• Inadequate volume assessment: Central venous pressure monitoring may be necessary to optimize fluid management 1
• Inappropriate use of nephrotoxic drugs: These should be strictly avoided in patients with advanced cirrhosis 2, 3
• Overlooking precipitating factors: Particularly bacterial infections which should be aggressively treated 1, 3