What is the appropriate workup for hypoalbuminemia?

Workup for Hypoalbuminemia

The workup for hypoalbuminemia should prioritize identifying inflammation as the primary cause rather than assuming malnutrition, followed by systematic evaluation for protein losses, liver dysfunction, and fluid overload. 1

Initial Assessment Framework

Step 1: Measure Inflammatory Markers

• Check C-reactive protein (CRP) immediately to distinguish inflammation-driven hypoalbuminemia from true protein depletion, as inflammatory cytokines directly downregulate hepatic albumin synthesis even with adequate protein intake 1, 2
• Recognize that albumin is a negative acute-phase reactant that decreases during any inflammatory state, making it primarily a marker of inflammation rather than nutritional status 1, 3
• Elevated CRP with low albumin strongly suggests inflammation as the primary driver 1

Step 2: Assess Hydration Status

• Evaluate for fluid overload clinically and with volume assessment, as hemodilution from excess fluid decreases serum albumin concentration 1, 2
• Over-hydration is particularly common in hospitalized and dialysis patients and can significantly lower measured albumin 1

Step 3: Evaluate for External Protein Losses

Renal losses:

• Measure urine albumin-to-creatinine ratio (uACR) to detect albuminuria 4
• Severely increased albuminuria (≥300 mg/g) with hypoalbuminemia and edema suggests nephrotic syndrome 4
• Check comprehensive metabolic panel including creatinine to assess kidney function 2

Gastrointestinal losses:

• Consider protein-losing enteropathy only when hypoalbuminemia persists despite treating inflammation, CRP is normal or mildly elevated, and there is no liver disease or nephrotic-range proteinuria 2
• Check stool studies if GI protein loss is suspected 1
• Measure vitamin B12, folate, and iron studies if malabsorption is suspected, particularly with small bowel disease 2

Step 4: Assess Hepatic Synthetic Function

• Check liver function tests (AST, ALT, bilirubin, INR) as hepatic synthetic dysfunction is a more common cause of hypoalbuminemia than GI losses 2
• Liver disease should be considered early in the differential 5

Additional Diagnostic Considerations

Evaluate Clinical Context

• Review comorbidities including cardiovascular disease, diabetes mellitus, and chronic kidney disease, as these independently contribute to hypoalbuminemia 1
• Consider age, as older patients tend to have lower baseline albumin levels 1
• Assess for metabolic acidosis, which can contribute to hypoalbuminemia 1

Nutritional Assessment

• Use validated nutritional screening tools (MUST, Mini Nutritional Assessment, or Subjective Global Assessment) rather than relying solely on albumin 1
• Body composition assessment is preferred over biochemical markers when diagnosing malnutrition 1
• Measure normalized protein nitrogen appearance (nPNA) in dialysis patients, targeting ≥0.9 g/kg/day 4

For Dialysis Patients Specifically

• Monitor serum albumin at least every 4 months 4
• Evaluate albumin in context of peritoneal transport type and delivered dialysis dose 4
• Consider prealbumin measurement given its shorter half-life 1

Critical Pitfalls to Avoid

• Do not assume hypoalbuminemia equals malnutrition - in most hospitalized patients, it reflects inflammation and disease severity rather than nutritional deficiency 1, 2, 3
• Do not order albumin infusions to "correct the number" - treat the underlying cause instead 2, 6
• Failing to recognize that albumin synthesis can be suppressed by catabolic illness even with adequate protein intake 4, 1
• Not considering multiple non-nutritional factors (inflammation, fluid status, protein losses) that affect albumin levels 1

Monitoring Frequency

• Every 1-3 months for patients with chronic inflammatory conditions or GI disease 2
• Every 3-6 months for vitamin B12 and folate in small bowel disease 2
• Every 4 months minimum for dialysis patients 4
• More frequent monitoring during acute illness or when albumin is declining 4