What are the etiologies of hypoalbuminemia (low serum albumin)?

Etiologies of Hypoalbuminemia (Low Serum Albumin)

Hypoalbuminemia has multiple etiologies including inflammation, malnutrition, protein losses, and fluid overload, with inflammation being the most significant contributor in many clinical scenarios. 1

Major Causes of Hypoalbuminemia

Inflammation

• Inflammatory cytokines (TNF-α, IL-6) directly downregulate albumin synthesis in the liver 1
• Inflammation causes the same changes in serum protein levels as protein-energy malnutrition, even with adequate caloric and protein intake 1
• C-reactive protein (CRP) and other positive acute-phase proteins are inversely correlated with serum albumin levels 1
• Inflammation may be the more powerful predictor of poor outcomes than low albumin itself 1

Nutritional Factors

• Poor energy and protein intake leads to decreased albumin synthesis 1
• Protein-energy malnutrition (PEM) is associated with higher rates of morbidity and mortality 1
• Serum albumin may fall modestly with sustained decrease in dietary protein and energy intake 1
• However, albumin is not an ideal marker of malnutrition as it's affected by many non-nutritional factors 2

External Protein Losses

• Nephrotic syndrome with significant albuminuria 3
• Protein-losing enteropathy with intestinal protein losses 2
• Peritoneal dialysis with albumin losses in dialysate 1
• Burns with exudative losses 3

Fluid Overload

• Hemodilution from excess fluid decreases serum albumin concentration 1
• Over-hydration is a common feature in dialysis patients that contributes to hypoalbuminemia 1
• Heart failure with fluid retention leads to dilutional hypoalbuminemia 4

Decreased Production

• Liver disease with reduced hepatocyte mass and function 5
• Cirrhosis leads to decreased albumin synthesis capacity 3
• Advanced and decompensated liver disease results in low albumin production 5

Increased Catabolism

• Enhanced rate of albumin turnover in various disease states 2
• Increased fractional catabolic rate during inflammation 6
• Catabolic and anabolic processes affect albumin levels 1

Other Contributing Factors

• Age - older patients tend to have lower albumin levels 1
• Comorbidities (cardiovascular disease, diabetes mellitus) 1
• Increased capillary permeability during sepsis or trauma leading to redistribution from vascular to interstitial space 2
• Metabolic acidosis can contribute to hypoalbuminemia 1

Clinical Significance

• Hypoalbuminemia is a powerful predictor of mortality in patients with chronic renal failure 6
• Low serum albumin is strongly associated with both mortality and cardiac disease in chronic kidney disease patients 1
• Hypoalbuminemia has emerged as an independent predictor of incident heart failure 4
• Hypoalbuminemia has a strong predictive value on mortality and morbidity regardless of cause 3

Assessment Approach

• Measure inflammatory markers (CRP, α1-acid glycoprotein) to identify inflammation in patients with low albumin 1
• Evaluate for protein-energy malnutrition when albumin is low 1
• Consider measuring prealbumin (transthyretin) which has a shorter half-life (2-3 days vs. 20 days for albumin) 1
• Assess for external protein losses (urine protein, stool studies) 1
• Evaluate hydration status as overhydration can dilute serum albumin concentration 1

Common Pitfalls

• Assuming hypoalbuminemia is solely due to malnutrition when inflammation may be the primary driver 1
• Failing to recognize that albumin is a negative acute-phase reactant that decreases during inflammation 7
• Not considering the multiple non-nutritional factors that affect serum albumin levels 1
• Simply administering albumin to patients with hypoalbuminemia has not been shown to improve survival or reduce morbidity in many cases 6
• Not recognizing that the cause of hypoalbuminemia, rather than low albumin levels specifically, may be responsible for morbidity and mortality 6