Purpose of Measuring Serum Protein
Serum protein measurements serve as complementary tools to assess nutritional status, predict clinical outcomes, and identify inflammation, with lower levels associated with higher risk of hospitalization and mortality, particularly in patients with chronic conditions such as kidney disease. 1
Primary Clinical Applications
- Serum albumin, the most commonly measured serum protein, is a powerful predictor of illness and death in patients with end-stage kidney disease (ESKD) and serves as a useful indicator of protein-energy nutritional status 1
- Serum prealbumin (transthyretin), with its shorter half-life (2-3 days vs. 20 days for albumin), can be more sensitive to rapid changes in nutritional status 1
- Serum proteins help identify patients at risk for protein-energy wasting (PEW), with serum albumin <3.5 g/dL associated with higher odds of mortality 1
- Glycated serum proteins (GSP) provide an index of glycemic status over a shorter period (1-2 weeks) compared to hemoglobin A1C (2-3 months), making them useful in situations where A1C may not be reliable 1
Interpretation Considerations
Serum proteins should not be interpreted in isolation as they are influenced by non-nutritional factors including: 1
- Inflammation or infection
- Hydration status
- Protein losses (urinary or dialysate)
- Acidemia
- Liver function
During inflammation, serum albumin and prealbumin decrease as negative acute-phase reactants, while positive acute-phase proteins (C-reactive protein, alpha-1 acid glycoprotein, ferritin) increase 1
Clinical Thresholds and Monitoring
- For maintenance dialysis patients, a predialysis or stabilized serum albumin equal to or greater than the lower limit of normal range (approximately 4.0 g/dL for the bromcresol green method) is the outcome goal 1
- Serum albumin <3.0 g/dL is associated with increased risk of surgical complications 2
- Routine monitoring of serum albumin is recommended monthly in dialysis patients 1
- Serum prealbumin <30 mg/dL should trigger evaluation for protein-energy malnutrition 1
Advanced Applications
- Serum proteomics has identified approximately 3700 distinct protein spots and 325 unique proteins in human serum, many serving as biomarkers for various diseases 3
- Protein modules in serum are associated with cardiovascular and metabolic disease states, as well as overall survival 4
- Mass spectrometry technologies have enabled detection of lower abundance serum proteins (ng/ml range) including human growth hormone, interleukin-12, and prostate-specific antigen 5
Common Pitfalls
- Assuming hypoalbuminemia is solely due to nutritional deficiency when inflammation may be the primary driver 6
- Failing to consider that serum protein levels may be insensitive to changes in nutritional status and do not necessarily correlate with changes in other nutritional parameters 1
- Not recognizing that serum proteins should be used as part of a comprehensive nutritional assessment rather than in isolation 1
- Overlooking that GSP values can vary with changes in the synthesis or clearance of serum proteins during acute illness or liver disease 1
For optimal assessment of nutritional status, guidelines recommend using serum proteins as part of a panel that includes other measures such as body weight assessment, subjective global assessment, dietary interviews, and normalized protein catabolic rate (nPCR) 1.