What is the Serum-Ascites Albumin Gradient (SAAG) and how is it used to diagnose the cause of ascites in a female patient?

What is SAAG (Serum-Ascites Albumin Gradient)?

SAAG is a diagnostic calculation that differentiates portal hypertension-related ascites from non-portal hypertension causes with approximately 97% accuracy by subtracting the ascitic fluid albumin concentration from the serum albumin concentration measured on the same day. 1, 2

How to Calculate SAAG

• Measure serum albumin and ascitic fluid albumin on the same day 3
• Subtract the ascitic fluid albumin value from the serum albumin value 3, 1
• Formula: SAAG = Serum Albumin - Ascitic Fluid Albumin 1

Interpretation of SAAG Values

High SAAG (≥1.1 g/dL) = Portal Hypertension Present

• A SAAG ≥1.1 g/dL indicates portal hypertension with 97% accuracy 3, 1, 2
• Common causes include:
  • Liver cirrhosis (most common) 3, 2
  • Cardiac ascites 3, 2
  • Hepatic vein thrombosis (Budd-Chiari syndrome) 3, 2
  • Sinusoidal obstruction syndrome (veno-occlusive disease) 3, 2

Low SAAG (<1.1 g/dL) = No Portal Hypertension

• A SAAG <1.1 g/dL suggests non-portal hypertension causes 1, 2
• Common causes include:
  • Peritoneal carcinomatosis 2, 4
  • Tuberculous peritonitis 3, 2
  • Nephrotic syndrome 1, 2
  • Pancreatic ascites 2

Clinical Utility: Why SAAG Matters

SAAG has replaced the older exudate/transudate classification system due to superior diagnostic accuracy 1, 5, 6

Treatment Implications Based on SAAG

• High SAAG patients (≥1.1 g/dL): Respond to sodium restriction (2000 mg/day) and diuretics (spironolactone 100 mg plus furosemide 40 mg daily) 1, 2
• Low SAAG patients (<1.1 g/dL): Generally do NOT respond to sodium restriction and diuretics (except nephrotic syndrome) and require treatment of the underlying disorder 1, 4

Distinguishing Cardiac from Cirrhotic Ascites

When SAAG is ≥1.1 g/dL, check the ascitic fluid protein concentration to differentiate causes: 2

• High SAAG + High protein (>2.5 g/dL) = Cardiac ascites 1, 2
• High SAAG + Low protein (<2.5 g/dL) = Cirrhotic ascites 2

This distinction is critical because both conditions cause portal hypertension but have different underlying pathophysiology and management approaches. 1

Initial Diagnostic Workup

The initial laboratory investigation of ascitic fluid should include: 1, 2

• Cell count with differential 3, 1
• Ascitic fluid total protein 3, 1
• SAAG calculation (requires simultaneous serum albumin) 3, 1
• If infection suspected: Culture fluid at bedside in blood culture bottles BEFORE antibiotics 1, 2

Critical Pitfalls and Caveats

Mixed Ascites (5% of Cases)

• Approximately 5% of patients have two or more causes of ascites simultaneously 1, 2
• Patients with portal hypertension PLUS a second cause still have SAAG ≥1.1 g/dL 1, 2
• Example: Cirrhosis patient who develops peritoneal carcinomatosis will maintain high SAAG 2

Low SAAG in Cirrhotic Patients

• In patients with known cirrhosis, a low SAAG (<1.1 g/dL) has low diagnostic yield—only 38% have an identifiable non-portal hypertension cause 7
• Recommendation: Repeat paracentesis, as 73% of cirrhotic patients with initial low SAAG convert to high SAAG on repeat testing 7
• This phenomenon likely reflects laboratory error, diuretic use, or sampling issues 7

Protein Concentration Matters for Risk Stratification

• Ascitic fluid protein <1.5 g/dL = High risk for spontaneous bacterial peritonitis (SBP) 4
• These patients may benefit from SBP prophylaxis 4

Never Order Serum CA-125

• CA-125 is nonspecifically elevated in ALL patients with ascites from any cause 2, 4
• Ordering this test leads to unnecessary gynecologic referrals and potentially fatal surgeries 2, 4

Special Diagnostic Considerations

• Tuberculous peritonitis: Ascitic fluid smear has 0-86% sensitivity; culture has only 20-57% sensitivity 3
• Adenosine deaminase (ADA) >32 U/L has 100% sensitivity and 96.6-100% specificity for tuberculous peritonitis in non-cirrhotic patients 3
• In cirrhotic patients with suspected tuberculosis, use lower ADA cutoff of 27 U/L (100% sensitivity, 93.3% specificity) 3