What are the diagnostic criteria for Hepatorenal Syndrome (HRS)?

Diagnostic Criteria for Hepatorenal Syndrome (HRS)

The diagnosis of hepatorenal syndrome requires cirrhosis with ascites, acute kidney injury according to International Club of Ascites criteria, no response after 2 consecutive days of diuretic withdrawal and plasma volume expansion with albumin (1 g/kg body weight), absence of shock, no current or recent use of nephrotoxic drugs, and no signs of structural kidney injury. 1

Current Diagnostic Criteria for HRS-AKI

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

AKI Staging in HRS Diagnosis

AKI is defined according to the following stages 1:

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

Evolution of HRS Diagnostic Criteria

The diagnostic criteria for HRS have evolved significantly over time. Previously, type 1 HRS required a doubling of serum creatinine to a value >2.5 mg/dL within 2 weeks 1. This rigid criterion has been removed in the updated guidelines because:

• It delayed potentially effective treatment until creatinine reached ≥2.5 mg/dL 1
• Higher serum creatinine at treatment initiation is associated with lower probability of response to vasoconstrictors and albumin 1, 2
• Earlier treatment leads to better outcomes 1, 3

Differential Diagnosis Considerations

In cirrhotic patients with AKI, HRS accounts for 15-43% of cases, while other common causes include 1:

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

Biomarkers are emerging as important tools for differential diagnosis:

• Urinary neutrophil gelatinase-associated lipocalin (NGAL) and other biomarkers (KIM-1, IL-18, L-FABP) may help differentiate HRS from acute tubular necrosis 1, 3
• These biomarkers are not yet part of routine clinical practice but show promise for future diagnostic algorithms 1

Pathophysiological Basis

HRS develops due to several mechanisms 4, 5:

• Splanchnic arterial vasodilation leading to reduced effective arterial blood volume 4
• Activation of sympathetic nervous system and renin-angiotensin-aldosterone system causing renal vasoconstriction 4
• Impaired cardiac function due to cirrhotic cardiomyopathy 4
• Inflammatory signals affecting proximal tubular cells 4, 6

Clinical Implications

• Early diagnosis is critical as HRS carries high mortality (median survival of untreated type 1 HRS is approximately 1 month) 1, 7
• Treatment with vasoconstrictors (terlipressin) plus albumin should be initiated promptly once diagnosis is established 1, 5
• Liver transplantation remains the definitive treatment for HRS 5, 3
• Prevention strategies include albumin infusion with antibiotics when treating spontaneous bacterial peritonitis 1, 5

Common Pitfalls in Diagnosis

• Incomplete fulfillment of diagnostic criteria (occurs in approximately 36% of cases in clinical practice) 7
• Failure to recognize HRS superimposed on organic nephropathy (occurs in approximately 8% of cases) 7
• Delayed diagnosis due to waiting for creatinine to reach arbitrary thresholds 1, 2
• Not considering HRS in patients with lower creatinine values who meet other criteria 1