What are the types of Hepatorenal Syndrome (HRS)?

Types of Hepatorenal Syndrome

Hepatorenal syndrome is classified into two distinct types: Type 1 HRS (now termed HRS-AKI) characterized by rapid, progressive renal impairment with serum creatinine increasing ≥100% to >2.5 mg/dL in less than 2 weeks, and Type 2 HRS (now termed HRS-CKD) featuring stable or slowly progressive renal impairment with a more chronic course. 1

Type 1 HRS (HRS-AKI)

• Rapid progression: Serum creatinine increases by at least 100% to a level >2.5 mg/dL within less than 2 weeks 1, 2
• Acute presentation: Often precipitated by a triggering event, most commonly bacterial infections (particularly spontaneous bacterial peritonitis), acute alcoholic hepatitis, or large-volume paracentesis without albumin replacement 1, 2
• Severe prognosis: Median survival of untreated Type 1 HRS is approximately 1 month, with some studies reporting as short as 2 weeks 1, 3
• Clinical manifestation: Presents as acute kidney injury with rapidly deteriorating renal function in the setting of advanced cirrhosis with ascites 1

Updated Nomenclature and Staging

• The International Club of Ascites now uses the term HRS-AKI instead of Type 1 HRS to align with modern nephrology terminology 1
• AKI staging follows specific criteria: Stage 1 (creatinine increase ≥0.3 mg/dL up to 2-fold baseline), Stage 2 (2-fold to 3-fold increase), Stage 3 (>3-fold increase or creatinine >4 mg/dL with acute increase ≥0.3 mg/dL or initiation of renal replacement therapy) 1
• Critical evolution: The fixed threshold of serum creatinine >1.5 mg/dL has been abandoned because it delays diagnosis and signifies severely reduced GFR; newer criteria emphasize dynamic changes rather than absolute values 1

Type 2 HRS (HRS-CKD)

• Chronic course: Features stable or less progressive impairment in renal function that develops over weeks to months 1, 2
• Better prognosis: Median survival of approximately 6 months, significantly longer than Type 1 HRS 3, 4
• Primary clinical feature: Refractory ascites is the dominant manifestation rather than acute renal failure 1, 5
• Spontaneous development: Often occurs without an obvious precipitating event, unlike Type 1 HRS 5

Updated Nomenclature

• Now termed HRS-CKD to reflect the chronic nature of kidney disease in these patients 2
• Represents a more stable form of renal dysfunction that may eventually progress to Type 1 HRS/HRS-AKI 6

Key Distinguishing Features

• Rate of progression: Type 1 develops over days to 2 weeks; Type 2 develops over weeks to months 1, 3
• Precipitating factors: Type 1 typically has identifiable triggers (infection, bleeding, hepatitis); Type 2 often lacks clear precipitants 5
• Survival without treatment: Type 1 has 1-2 weeks median survival; Type 2 has 6 months median survival 3, 4
• Primary clinical problem: Type 1 presents as acute renal failure; Type 2 presents as refractory ascites 5

Common Pitfall to Avoid

• Do not wait for creatinine to reach 1.5 mg/dL before considering HRS—this outdated criterion has been removed because it delays diagnosis and treatment, which directly impacts outcomes 1
• Earlier treatment leads to better outcomes, particularly in Type 1 HRS where every day counts given the 1-month median survival 1

Clinical Context for Both Types

• HRS accounts for only 15-43% of AKI cases in cirrhotic patients; other causes include hypovolemia (27-50%) and acute tubular necrosis (14-35%), making differential diagnosis critical 1
• Approximately 30% of patients with spontaneous bacterial peritonitis develop HRS, making infection the most important risk factor 1
• Both types require the same diagnostic criteria: cirrhosis with ascites, no response after 2 days of diuretic withdrawal and albumin expansion (1 g/kg), absence of shock, no nephrotoxic drugs, and no structural kidney injury 1, 7