What is the appropriate workup for a patient presenting with hypoalbuminemia (low albumin levels)?

Workup for Hypoalbuminemia

Recognize That Albumin Is Primarily a Marker of Inflammation, Not Malnutrition

The most critical first step is measuring C-reactive protein (CRP) to determine whether hypoalbuminemia reflects systemic inflammation rather than true protein loss or malnutrition. 1 This distinction fundamentally changes your diagnostic approach, as inflammatory cytokines directly downregulate hepatic albumin synthesis even when protein and caloric intake are adequate 2, 3.

Initial Laboratory Assessment

Essential First-Line Tests

• Comprehensive metabolic panel to assess liver synthetic function (other coagulation factors, bilirubin) and identify hepatic dysfunction as a cause 1
• C-reactive protein to quantify the inflammatory burden—albumin and CRP are inversely correlated 2
• Urinalysis with urine albumin-to-creatinine ratio (uACR) to detect nephrotic-range proteinuria (≥300 mg/g suggests nephrotic syndrome) 2
• Complete blood count to assess for anemia from malabsorption or chronic disease 1

Assess for Fluid Overload

• Clinical volume status examination is critical, as hemodilution from excess fluid decreases serum albumin concentration independent of true protein depletion 1, 2
• Over-hydration is particularly common in hospitalized patients and dialysis patients 2

Algorithm for Determining the Cause

If CRP is Elevated (Inflammation-Driven)

• Do not assume malnutrition—in most hospitalized patients, hypoalbuminemia reflects inflammation and disease severity rather than nutritional deficiency 1, 2, 3
• Focus on identifying and treating the underlying inflammatory condition (infection, IBD, malignancy, autoimmune disease) 1
• Albumin levels will improve as inflammation resolves, not from albumin infusions 4, 3

If CRP is Normal or Mildly Elevated AND Liver/Kidney Function Normal

Consider protein-losing enteropathy when hypoalbuminemia persists despite treating inflammation, CRP is normal or only mildly elevated, and there is no evidence of liver disease or nephrotic-range proteinuria 1

GI-Specific Workup for Suspected Protein Loss

• Iron studies including ferritin and transferrin saturation to assess for malabsorption 1
• Vitamin B12 and folate levels, particularly if small bowel disease or prior resection is suspected (monitor every 3-6 months in at-risk patients) 1
• Stool alpha-1 antitrypsin clearance or fecal protein loss studies if protein-losing enteropathy is suspected 2
• Consider endoscopy if GI symptoms are present or malabsorption markers are abnormal 1

If Nephrotic-Range Proteinuria Present

• Severely increased albuminuria (≥300 mg/g) with hypoalbuminemia and edema indicates nephrotic syndrome requiring nephrology referral 2
• Further workup includes renal biopsy consideration, complement levels, serology for secondary causes 2

If Liver Dysfunction Present

• Hepatic synthetic dysfunction is a more common cause than GI losses 1
• Assess for cirrhosis with imaging, additional coagulation studies, and hepatology consultation 1

Critical Pitfalls to Avoid

• Never assume hypoalbuminemia equals malnutrition—inflammation alters visceral protein homeostasis causing albumin to decline even with adequate intake 1, 2, 4, 3
• Do not order albumin infusions to "correct" the number—treat the underlying cause instead 1, 4
• Failing to recognize albumin as a negative acute-phase reactant that decreases during inflammation regardless of nutritional status 2, 3
• Not considering multiple non-nutritional factors including age, comorbidities, metabolic acidosis, and catabolic states 2

Monitoring During Workup

• Monitor albumin and inflammatory markers every 1-3 months in patients with chronic disease 1
• Monitor vitamin B12 and folate every 3-6 months in small bowel disease or post-resection 1
• Monitor iron studies every 3 months in symptomatic IBD patients 1
• Increasing or decreasing serum albumin levels are adequate indicators of clinical improvement or deterioration 3

Nutritional Support During Workup

While investigating the cause, initiate nutritional support immediately providing at least 30g protein daily, targeting 1.2-1.5 g/kg/day through diet and supplements 1. However, recognize that nutrition support cannot fully correct hypoalbuminemia if the underlying inflammatory process remains untreated 3.