Hepatorenal Syndrome Types
Hepatorenal syndrome is classified into two distinct types: Type 1 HRS (now termed HRS-AKI) characterized by rapid, progressive renal impairment, and Type 2 HRS (now termed HRS-CKD) featuring a more stable, chronic course of kidney dysfunction. 1, 2, 3
Type 1 HRS (HRS-AKI)
Type 1 HRS represents the acute, severe form with rapid progression and extremely poor prognosis if untreated. 1, 3
Clinical Characteristics
Rapid, progressive renal impairment with serum creatinine increasing ≥100% to >2.5 mg/dL in less than 2 weeks (using older criteria), though newer criteria emphasize dynamic AKI staging rather than fixed thresholds 3, 4
Median survival of approximately 1 month without treatment, making this one of the most severe forms of AKI in cirrhotic patients 2, 3, 5
Frequently triggered by bacterial infections, particularly spontaneous bacterial peritonitis, which precipitates HRS in approximately 30% of cases 2, 3
Modern AKI Staging Criteria
The International Club of Ascites now uses dynamic AKI staging rather than fixed creatinine thresholds 1, 3:
- Stage 1: Creatinine increase ≥0.3 mg/dL within 48 hours or 1.5-2× baseline 1
- Stage 2: Creatinine 2-3× baseline 1
- Stage 3: Creatinine >3× baseline or >4 mg/dL with acute increase ≥0.3 mg/dL, or initiation of renal replacement therapy 1
The fixed threshold of serum creatinine >1.5 mg/dL has been abandoned because it delays diagnosis and signifies severely reduced GFR—earlier treatment leads to better outcomes. 3
Type 2 HRS (HRS-CKD)
Type 2 HRS represents the chronic form with more stable kidney dysfunction and longer survival compared to Type 1. 1, 3
Clinical Characteristics
Stable or slowly progressive renal impairment with moderate kidney dysfunction rather than acute deterioration 3, 4
Median survival of approximately 6 months, significantly longer than Type 1 HRS 5, 6
Main clinical manifestation is refractory ascites that responds poorly to diuretic therapy 5
More stable clinical condition makes patients better candidates for transjugular intrahepatic portosystemic shunt (TIPS), which has been shown to improve both renal function and ascites control 1
Key Pathophysiological Distinction
Both types share the same underlying mechanism—extreme splanchnic vasodilation leading to decreased effective arterial volume, triggering compensatory renal vasoconstriction—but differ in the rapidity and severity of progression 1, 3, 7:
Type 1 HRS involves an abrupt, severe hemodynamic decompensation, often precipitated by infection or other acute insults 4, 7
Type 2 HRS represents a more gradual progression of circulatory dysfunction without acute triggers 3, 6
Critical Diagnostic Considerations
Both types require the same diagnostic criteria established by the International Club of Ascites 1, 3:
- Cirrhosis with ascites 3
- No improvement after 2 consecutive days of diuretic withdrawal and albumin expansion (1 g/kg, maximum 100 g) 1, 3
- Absence of shock, nephrotoxic drugs, and structural kidney disease 1, 3
- No proteinuria >500 mg/day or microhematuria >50 RBCs/HPF 3
- Normal renal ultrasonography 3
The distinction between Type 1 HRS and acute tubular necrosis remains challenging with current clinical tools, though biomarkers such as urinary NGAL, KIM-1, IL-18, and L-FABP may help differentiate these conditions. 3, 8
Treatment Implications by Type
Type 1 HRS requires urgent vasoconstrictor therapy (terlipressin or norepinephrine plus albumin) and expedited liver transplantation referral, with treatment success rates of 64-76% when terlipressin is used 1, 2
Type 2 HRS management focuses on controlling ascites, with TIPS being more applicable due to the more stable clinical condition, though liver transplantation remains the definitive treatment for both types 1, 2