What are the diagnostic criteria for hepatorenal syndrome?

Diagnostic Criteria for Hepatorenal Syndrome

Hepatorenal syndrome (HRS) is diagnosed when a patient with cirrhosis and ascites develops acute kidney injury (AKI) that fails to improve after 2 consecutive days of diuretic withdrawal and albumin volume expansion (1 g/kg body weight), in the absence of shock, nephrotoxic drugs, or structural kidney disease. 1

Core Diagnostic Requirements

The International Club of Ascites consensus criteria require ALL of the following 2, 1:

• Cirrhosis with ascites 1
• AKI defined by ICA-AKI criteria (see staging below) 1
• No improvement in serum creatinine after 2 consecutive days of:
  • Diuretic withdrawal AND
  • Plasma volume expansion with albumin 1 g/kg body weight (maximum 100 g/day) 1, 3
• Absence of shock 1
• No current or recent nephrotoxic drug use (NSAIDs, aminoglycosides, iodinated contrast media) 1
• No evidence of structural kidney injury:
  • Proteinuria <500 mg/day 1
  • Microhematuria <50 RBCs per high power field 1
  • Normal renal ultrasonography 1

AKI Staging System

The American Association for the Study of Liver Diseases recommends the following staging 1:

• Stage 1: Creatinine increase ≥0.3 mg/dL OR up to 2-fold from baseline 1
• Stage 2: Creatinine increase 2-fold to 3-fold from baseline 1
• Stage 3: Creatinine increase >3-fold from baseline OR creatinine >4 mg/dL with acute increase ≥0.3 mg/dL OR initiation of renal replacement therapy 1

Critical Evolution from Old Criteria

The fixed threshold of serum creatinine >1.5 mg/dL (133 µmol/L) has been abandoned because it often signifies severely reduced GFR (~30 mL/min) and delays diagnosis. 2 The newer criteria emphasize dynamic changes in creatinine rather than absolute values, allowing earlier detection and treatment. 2

The old requirement of doubling serum creatinine to >2.5 mg/dL within 2 weeks for type 1 HRS has been removed to enable earlier intervention. 1 This change is critical because earlier treatment leads to better outcomes, and median survival of untreated type 1 HRS is only approximately 1 month. 2, 1

Differential Diagnosis Considerations

HRS accounts for only 15-43% of AKI cases in cirrhotic patients. 1 Other common causes include:

• Hypovolemia: 27-50% of cases 1
• Acute tubular necrosis (ATN): 14-35% of cases 1

Urinary neutrophil gelatinase-associated lipocalin (NGAL) and other biomarkers (KIM-1, IL-18, L-FABP) may help differentiate HRS from ATN. 1 This distinction is crucial because management differs significantly.

Common Pitfalls to Avoid

• Do not wait for creatinine to reach 1.5 mg/dL before considering HRS—use the dynamic AKI criteria instead 2
• Do not rely on urine output as a diagnostic criterion in cirrhotic patients with ascites, as they are frequently oliguric despite normal GFR or may have increased output from diuretics 2
• Always exclude volume depletion adequately with the 2-day albumin trial before diagnosing HRS 1
• Consider renal biopsy if proteinuria, microhematuria, or abnormal kidney size is present to evaluate for parenchymal disease and guide combined liver-kidney transplant decisions 2

Clinical Context

Bacterial infections, particularly spontaneous bacterial peritonitis (SBP), are the most important risk factor—HRS develops in approximately 30% of patients with SBP. 2, 1 High MELD scores and type 1 HRS (now termed HRS-AKI) carry very poor prognosis with median survival of approximately 3 months overall and 1 month for untreated type 1 HRS. 2, 1