What are the criteria for diagnosing hepatorenal syndrome?

Diagnostic Criteria for Hepatorenal Syndrome

The diagnosis of hepatorenal syndrome requires the presence of cirrhosis with ascites, acute kidney injury according to established criteria, no response to albumin volume expansion after diuretic withdrawal, absence of shock, no recent use of nephrotoxic drugs, and no evidence of structural kidney injury. 1

Current Diagnostic Criteria for HRS

All of the following criteria must be met for HRS diagnosis:

• Presence of cirrhosis and ascites 2, 1
• Diagnosis of acute kidney injury according to KDIGO criteria 2, 1
• No response after 2 consecutive days of diuretic withdrawal and plasma volume expansion with albumin (1 g/kg body weight) 2, 1
• Absence of shock 2, 1
• No current or recent use of nephrotoxic drugs (NSAIDs, aminoglycosides, iodinated contrast media) 2, 1
• No signs of structural kidney injury, defined as:
  • Absence of proteinuria (>500 mg/day) 2, 1
  • Absence of microhematuria (>50 red blood cells per high power field) 2, 1
  • Normal findings on renal ultrasonography 2, 1

AKI Staging in HRS Diagnosis

The International Club of Ascites recommends using AKI staging for HRS diagnosis 2, 1:

• Stage 1: Increase in serum creatinine ≥0.3 mg/dL up to 2-fold of baseline 1
• Stage 2: Increase in serum creatinine between 2-fold and 3-fold of baseline 1
• Stage 3: Increase in serum creatinine >3-fold of baseline or creatinine >4 mg/dL with an acute increase ≥0.3 mg/dL or initiation of renal replacement therapy 1

Classification of HRS

HRS is classified into two types based on the progression of renal impairment:

• Type 1 HRS (now termed HRS-AKI): Characterized by rapidly progressive renal failure with doubling of serum creatinine to >2.5 mg/dL in less than 2 weeks 3, 4
• Type 2 HRS: Characterized by more stable or slowly progressive renal impairment 3

Evolution of Diagnostic Criteria

The diagnostic criteria for HRS have evolved over time:

• Earlier criteria required a serum creatinine threshold of >1.5 mg/dL (133 μmol/L) 2
• Current criteria focus on changes in serum creatinine rather than absolute values, allowing for earlier diagnosis and treatment 2, 1, 4
• The requirement for a doubling of serum creatinine to a value >2.5 mg/dL within 2 weeks for type 1 HRS has been removed in updated guidelines 1, 5

Differential Diagnosis Considerations

HRS must be differentiated from other causes of acute kidney injury in cirrhosis:

• HRS accounts for 15-43% of AKI cases in cirrhotic patients 1
• Other common causes include hypovolemia (27-50%) and acute tubular necrosis (14-35%) 1, 6
• Biomarkers such as urinary neutrophil gelatinase-associated lipocalin (NGAL) may help differentiate HRS from acute tubular necrosis 1, 6
• Serum cystatin C may identify early renal dysfunction in patients with normal creatinine levels 7

Clinical Implications

• Early diagnosis is critical as HRS carries high mortality (median survival of untreated type 1 HRS is approximately 1 month) 2, 3
• Treatment with vasoconstrictors (terlipressin) plus albumin is the standard of care 3, 6
• Terlipressin is typically administered at an initial dose of 1 mg IV every 4-6 hours, increased stepwise to maximum 2 mg every 4 hours if serum creatinine doesn't decrease by at least 25% after 3 days 3
• Continuous infusion of terlipressin (2-12 mg/day) may be as effective as bolus administration with fewer adverse events 2, 4
• Liver transplantation remains the definitive treatment for HRS 3, 1

Prevention Strategies

• Albumin infusion with antibiotics when treating spontaneous bacterial peritonitis 2, 3
• Norfloxacin (400 mg/day) can reduce HRS incidence in advanced cirrhosis 3
• Pentoxifylline (400 mg three times daily) can prevent HRS in severe alcoholic hepatitis 3
• Avoiding nephrotoxic drugs in patients with advanced cirrhosis 3, 1