What is the diagnostic approach for hepatorenal syndrome?

Diagnosis of Hepatorenal Syndrome

Hepatorenal syndrome (HRS) is diagnosed by confirming cirrhosis with ascites, serum creatinine >1.5 mg/dL, no improvement after diuretic withdrawal and volume expansion with albumin, absence of shock, no current/recent nephrotoxic drug exposure, and absence of parenchymal kidney disease. 1

Diagnostic Criteria

The diagnosis of HRS requires all of the following criteria:

• Advanced chronic or acute liver failure with portal hypertension 2
• Serum creatinine greater than 1.5 mg/dL or 24-hour creatinine clearance less than 40 mL per minute 2
• No improvement in renal function following:
  • Diuretic withdrawal 1
  • Expansion of plasma volume with 1.5 L of isotonic saline or albumin (1 g/kg body weight) 2, 1
• Absence of shock 2, 1
• No current or recent treatment with nephrotoxic drugs 2, 1
• Less than 500 mg/dL proteinuria 2
• No ultrasonographic evidence of obstructive uropathy or parenchymal kidney disease 2, 1

Classification of HRS

HRS is classified into two types:

• Type 1 HRS (HRS-AKI):

  • Rapidly progressive renal impairment 1
  • Doubling of initial serum creatinine to >2.5 mg/dL or 50% reduction of creatinine clearance to <20 mL/min in less than 2 weeks 2
  • Poor prognosis with median survival of approximately 1 month if untreated 1

• Type 2 HRS:

  • Stable or slowly progressive renal impairment 1
  • More chronic course with better survival compared to Type 1 HRS 1

Diagnostic Approach

1. Rule out other causes of acute kidney injury: 3

   • Prerenal azotemia (responds to volume expansion)
   • Acute tubular necrosis (history of shock, nephrotoxic drugs)
   • Sepsis-induced renal failure

2. Perform diagnostic paracentesis: 2, 4

   • Essential to rule out spontaneous bacterial peritonitis (SBP)
   • SBP is diagnosed when ascitic fluid has:
     • Positive bacterial culture
     • Elevated PMN count ≥250 cells/mm³ (0.25 x 10⁹/L)

3. Laboratory evaluation:

   • Serum creatinine >1.5 mg/dL 1
   • Urine analysis: <500 mg/dL proteinuria, absence of microhematuria (<50 RBCs per high power field) 2
   • Urinary biomarkers: Consider urinary neutrophil gelatinase-associated lipocalin to differentiate from acute tubular necrosis 5

4. Imaging:

   • Renal ultrasonography to exclude obstructive uropathy and parenchymal kidney disease 2, 1

5. Volume expansion test:

   • Withdraw diuretics for at least 2 days 1
   • Administer albumin 1 g/kg body weight 2, 1
   • Lack of improvement in renal function supports HRS diagnosis 1

Diagnostic Pitfalls and Challenges

• In approximately 36% of cases, HRS may be presumed because not all diagnostic criteria can be fulfilled 6
• HRS can be superimposed on organic nephropathy in about 8% of cases 6
• Ischemic or toxic tubular necrosis or sepsis may cause renal failure in cirrhotic patients and must be differentiated from HRS 3
• Uncontrolled HRS may progress to ischemic tubular necrosis, requiring early management in an intensive care unit 3
• Diagnostic paracentesis is essential as ascitic fluid infection is common in cirrhotic patients with ascites and can trigger HRS 2, 4

Prognostic Factors

• Age, bilirubin levels, and creatinine increase after diagnostic volume expansion independently predict mortality 6
• Patients with at least two negative predictors have a mortality rate of approximately 97% 6
• Type 1 HRS has a 3-month survival rate of only about 19.7% without appropriate treatment 6

Early diagnosis of HRS is crucial as it allows for timely intervention with vasoconstrictors and albumin, which can improve outcomes and serve as a bridge to liver transplantation, the definitive treatment for this condition 1, 4, 7.