Diagnostic Criteria for Hepatorenal Syndrome
The diagnosis of hepatorenal syndrome requires cirrhosis with ascites, acute kidney injury defined by ICA-AKI criteria (increase in creatinine ≥0.3 mg/dL), no improvement after 2 consecutive days of diuretic withdrawal and volume expansion with albumin (1 g/kg body weight up to 100 g/day), absence of shock, no current or recent nephrotoxic drug use, and absence of structural kidney disease (proteinuria <500 mg/day, microhematuria <50 RBCs/HPF, normal renal ultrasound). 1
Core Diagnostic Requirements
The International Club of Ascites updated criteria in 2007 represent a critical evolution from older definitions. The fixed threshold of serum creatinine >1.5 mg/dL has been abandoned because it delays diagnosis and signifies severely reduced GFR—the newer criteria emphasize dynamic changes in creatinine rather than absolute values, allowing earlier detection and treatment. 1
Essential Criteria (All Must Be Present)
Cirrhosis with ascites - This is the foundational requirement for HRS diagnosis 2, 1
Acute kidney injury by ICA-AKI criteria - Stage 1: creatinine increase ≥0.3 mg/dL up to 2-fold baseline; Stage 2: 2-fold to 3-fold baseline; Stage 3: >3-fold baseline or creatinine >4 mg/dL with acute increase ≥0.3 mg/dL or initiation of renal replacement therapy 1, 3
No response to volume challenge - No improvement in serum creatinine (decrease to ≤1.5 mg/dL) after at least 2 days with diuretic withdrawal and albumin expansion at 1 g/kg body weight/day up to maximum 100 g/day 2, 1
Absence of shock - Hemodynamic stability must be documented 2, 1
No nephrotoxic drug exposure - No current or recent treatment with NSAIDs, aminoglycosides, iodinated contrast media, or other nephrotoxic agents 2, 1
Absence of structural kidney disease - Proteinuria <500 mg/day, microhematuria <50 red blood cells per high power field, and normal renal ultrasonography findings 2, 1
Classification of HRS Types
Type 1 HRS (HRS-AKI) is characterized by rapidly progressive renal impairment with serum creatinine increasing ≥100% to >2.5 mg/dL in less than 2 weeks, carrying a median survival of approximately 1 month if untreated. 2, 1
Type 2 HRS (HRS-CKD) features stable or less progressive impairment in renal function with a more chronic course and better survival compared to Type 1. 3
Critical Pitfalls to Avoid
Do not wait for creatinine to reach 1.5 mg/dL before considering HRS—use the dynamic AKI criteria instead. The older 2004 criteria required serum creatinine >1.5 mg/dL, but this approach has been superseded because earlier treatment leads to better outcomes. 2, 1
Do not rely on urine output as a diagnostic criterion in cirrhotic patients with ascites, as these patients often have complex fluid dynamics that make urine output an unreliable marker. 1
Consider that HRS accounts for only 15-43% of AKI cases in cirrhotic patients—other common causes include hypovolemia (27-50% of cases) and acute tubular necrosis (14-35% of cases). 1 Differentiating these conditions is essential because vasoconstrictors are not justified for ATN treatment. 4
Differential Diagnosis Tools
Urinary biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), KIM-1, IL-18, and L-FABP may help differentiate HRS from acute tubular necrosis. 1, 5 These biomarkers provide additional diagnostic precision beyond traditional criteria.
Inferior vena cava ultrasound may reveal persistent intravascular hypovolemia or hypervolemia that contributes to AKI despite standardized albumin administration, potentially identifying HRS misdiagnosis in up to 40% of cases. 6 IVC collapsibility index ≥50% with IVCmax ≤0.7 cm suggests hypovolemia requiring additional volume; IVC-CI <20% with IVCmax >0.7 cm suggests hypervolemia requiring diuretics. 6
Clinical Context and Risk Factors
Bacterial infections, particularly spontaneous bacterial peritonitis (SBP), are the most important risk factor—HRS develops in approximately 30% of patients with SBP. 1, 7 Prevention with albumin infusion (1.5 g/kg at diagnosis, 1 g/kg on day 3) plus antibiotics during SBP treatment significantly reduces HRS incidence. 3
Consider renal biopsy if proteinuria, microhematuria, or abnormal kidney size is present to evaluate for parenchymal disease and guide combined liver-kidney transplant decisions. 1