What are the diagnostic criteria and treatment options for hepatorenal syndrome in a patient with cirrhosis or advanced liver disease and impaired renal function?

Hepatorenal Syndrome Diagnostic Criteria

Hepatorenal syndrome is diagnosed when a patient with cirrhosis and ascites develops acute kidney injury (defined as creatinine increase ≥0.3 mg/dL within 48 hours or ≥50% from baseline) that fails to improve after 2 consecutive days of diuretic withdrawal and albumin expansion (1 g/kg, maximum 100 g), in the absence of shock, nephrotoxic drugs, structural kidney disease (proteinuria >500 mg/day, microhematuria >50 RBCs/HPF), or abnormal renal ultrasound. 1, 2

Evolution from Traditional Criteria

The diagnostic approach has fundamentally shifted from the older 2004 criteria. The fixed serum creatinine threshold of >1.5 mg/dL has been abandoned because it delays diagnosis—by the time creatinine reaches 1.5 mg/dL, GFR is often already severely reduced to approximately 30 mL/min. 1, 2 The newer International Club of Ascites (ICA) criteria from 2015 emphasize dynamic changes in creatinine rather than absolute values, allowing earlier detection and treatment initiation. 1

Complete Diagnostic Criteria Checklist

All five major criteria must be present: 1, 2

• Advanced chronic or acute liver failure with portal hypertension and ascites 1
• Acute kidney injury meeting ICA-AKI criteria (creatinine increase ≥0.3 mg/dL within 48 hours OR ≥50% increase from baseline) 1, 2
• No sustained improvement in renal function after 2 consecutive days of diuretic withdrawal AND plasma volume expansion with albumin 1 g/kg (maximum 100 g on day 1) 1, 2
• Absence of shock, ongoing bacterial infection, and no current or recent nephrotoxic drug exposure (NSAIDs, aminoglycosides, iodinated contrast) 1, 2
• No evidence of structural kidney disease: proteinuria <500 mg/day, microhematuria <50 RBCs per high-power field, and normal renal ultrasonography 1, 2

AKI Staging System

The diagnosis now incorporates AKI staging to guide urgency and prognosis: 3, 2

• Stage 1: Creatinine increase ≥0.3 mg/dL or 1.5-2× baseline 3, 2
• Stage 2: Creatinine 2-3× baseline 3, 2
• Stage 3: Creatinine >3× baseline OR >4 mg/dL with acute increase ≥0.3 mg/dL OR initiation of renal replacement therapy 3, 2

Classification: Type 1 vs Type 2 HRS

Type 1 HRS (now termed HRS-AKI) is characterized by rapidly progressive renal impairment with doubling of serum creatinine to >2.5 mg/dL or 50% reduction in creatinine clearance to <20 mL/min within less than 2 weeks, carrying a median survival of approximately 1 month if untreated. 1, 3, 2

Type 2 HRS features stable or less progressive renal dysfunction with a more chronic course and better survival compared to Type 1. 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, as earlier treatment leads to better outcomes. 1, 2 Do not rely on urine output as a diagnostic criterion in cirrhotic patients with ascites, since these patients are frequently oliguric with avid sodium retention yet may maintain relatively normal GFR. 1

Always perform diagnostic paracentesis to exclude spontaneous bacterial peritonitis (SBP), which precipitates HRS in approximately 30% of cases and requires specific treatment with antibiotics plus albumin. 3, 2, 4

Differential Diagnosis Context

HRS accounts for only 15-43% of AKI cases in cirrhotic patients. 2 Other common causes include:

• Hypovolemia (27-50% of cases)—responds to volume expansion 2, 4
• Acute tubular necrosis (14-35% of cases)—involves structural kidney damage 2, 4

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

Treatment Implications

Once HRS is diagnosed, treatment with vasoconstrictors plus albumin should be initiated immediately. 4 The first-line treatment is terlipressin 1 mg IV every 4-6 hours (increased to 2 mg every 4 hours if creatinine doesn't decrease by ≥25% after 3 days) plus albumin 1 g/kg on day 1 (maximum 100 g), then 20-40 g/day. 3, 4, 5 In regions where terlipressin is unavailable, midodrine (titrated to 12.5 mg orally three times daily) plus octreotide (200 μg subcutaneously three times daily) plus albumin is an alternative. 3, 4

Liver transplantation remains the definitive treatment, with expedited referral recommended for all Type 1 HRS patients, achieving approximately 65% post-transplant survival. 3, 4