What Causes Low Albumin (Hypoalbuminemia)
Inflammation is the primary driver of hypoalbuminemia in most clinical contexts, directly suppressing hepatic albumin synthesis through inflammatory cytokines, even when protein and caloric intake are adequate. 1
Primary Mechanisms of Hypoalbuminemia
Inflammation (Most Common Cause)
- Inflammatory cytokines directly downregulate albumin synthesis in the liver, regardless of nutritional status. 1
- C-reactive protein and other positive acute-phase proteins are inversely correlated with serum albumin levels. 1
- The acute-phase response causes albumin synthesis to decrease as the liver reprioritizes production toward inflammatory proteins. 1
- Inflammation increases the fractional catabolic rate (FCR) of albumin, accelerating its breakdown. 2
- Critical illness and postoperative states typically show a 10-15 g/L decrease in albumin due to inflammatory cytokines and transcapillary loss. 1
Renal Protein Losses
- Nephrotic syndrome causes massive urinary albumin losses (>3.8 g/day), with severely increased albuminuria presenting alongside hypoalbuminemia and edema. 3, 1
- The primary causes in nephrotic patients are urinary albumin losses combined with an inappropriately increased fractional catabolic rate and insufficient compensatory synthesis. 4
- Peritoneal dialysis patients lose albumin in dialysate, contributing significantly to hypoalbuminemia. 1, 4
Decreased Hepatic Synthesis
- Liver cirrhosis and chronic liver disease directly impair albumin production capacity. 1
- Liver congestion from heart failure reduces synthetic capacity. 1
- In hemodialysis patients, reduced albumin synthesis results from inflammation (acute-phase response) combined with inadequate nutrition. 4, 5
- Albumin synthesis correlates negatively with inflammatory markers (alpha-2-macroglobulin, C-reactive protein). 5
Gastrointestinal Losses
- Protein-losing enteropathy causes gastrointestinal albumin losses. 1, 6
- Malabsorption syndromes contribute to hypoalbuminemia. 1
Hemodilution
- Excess fluid volume decreases serum albumin concentration through dilution. 1
- Over-hydration is a common feature in dialysis patients that contributes to hypoalbuminemia. 1
Increased Catabolism
- Corticosteroids increase net protein loss and drive catabolism, contributing to hypoalbuminemia. 7
- Catabolic illness suppresses albumin synthesis even with adequate protein intake. 1
Disease-Specific Contexts
Heart Failure
- Hypoalbuminemia results from malnutrition, inflammation, cachexia, hemodilution, liver dysfunction, protein-losing enteropathy, increased transcapillary escape rate, and nephrotic syndrome. 6
- Low plasma oncotic pressure induces fluid shift from intravascular to interstitial space, facilitating cardiogenic pulmonary edema. 6
Chronic Kidney Disease and Dialysis
- In hemodialysis patients, hypoalbuminemia results primarily from reduced albumin synthesis due to inflammation, not from external losses. 4, 5
- Albumin synthesis rate correlates negatively with inflammatory markers and positively with IGF-1. 5
- CAPD patients can increase albumin synthesis to replace losses, unlike hemodialysis patients. 4
Nephrotic Syndrome
- Urinary albumin losses exceed 3.8 g/day, creating a 35% risk of end-stage renal disease within 2 years. 3
- A T-cell-driven circulating factor interferes with glomerular permselectivity to albumin. 3
Contributing Factors
Age and Comorbidities
- Older patients tend to have lower albumin levels. 1
- Comorbidities such as cardiovascular disease and diabetes mellitus contribute to hypoalbuminemia. 1
- Elderly patients have higher rates of renal failure, malnutrition, malignancies, and frailty that compound hypoalbuminemia risk. 1
Metabolic Factors
- Metabolic acidosis can contribute to hypoalbuminemia. 1
- Longer hospital stays are independently associated with hypoalbuminemia development, reflecting disease severity and heightened inflammation. 1
Clinical Significance
A decrease of 1.0 g/dL in serum albumin increases the odds of morbidity by 89% and mortality by 137%. 3, 7
- Low serum albumin is strongly associated with both mortality and cardiac disease in chronic kidney disease patients. 1
- Serum albumin <35 g/L is associated with decreased survival in hospitalized patients. 1
- In dialysis patients, death risk increases by 6% for every 0.1 g/dL decrease in serum albumin. 7
Critical Pitfall to Avoid
The most common error is assuming hypoalbuminemia is solely due to malnutrition when inflammation is actually the primary driver. 1, 7 Albumin is a negative acute-phase reactant that decreases during inflammation regardless of nutritional status. 1 Measuring C-reactive protein or other inflammatory markers helps distinguish inflammation-driven hypoalbuminemia from pure malnutrition. 1, 7