How to manage low albumin (hypoalbuminemia) levels?

Management of Hypoalbuminemia

The primary approach to managing hypoalbuminemia is to identify and treat the underlying cause—particularly inflammation, inadequate nutrition, protein losses, and fluid overload—rather than simply administering albumin, except in specific liver disease scenarios where albumin infusion has proven mortality benefit. 1, 2

Understanding the Pathophysiology

Hypoalbuminemia results from multiple mechanisms that must be addressed simultaneously:

• Inflammation is the dominant driver in most clinical contexts, as inflammatory cytokines directly downregulate hepatic albumin synthesis even when protein and caloric intake are adequate 1, 3
• Protein-energy malnutrition contributes through sustained decrease in dietary protein and energy intake, though albumin falls only modestly from this alone 1
• External protein losses occur through urinary losses (nephrotic syndrome, diabetic nephropathy) or dialysate losses in peritoneal dialysis 1, 4
• Hemodilution from fluid overload decreases serum albumin concentration without true albumin depletion 1
• Increased catabolism from acute illness, metabolic acidosis, or corticosteroid use accelerates albumin degradation 5, 1

Critical pitfall: Assuming hypoalbuminemia is solely due to malnutrition when inflammation is often the primary driver—albumin is a negative acute-phase reactant that decreases during inflammation regardless of nutritional status 1, 3

Diagnostic Evaluation

Initial Assessment

• Measure inflammatory markers (C-reactive protein) to distinguish inflammation-driven hypoalbuminemia from pure malnutrition 1
• Assess for external protein losses: urine albumin-to-creatinine ratio (uACR) to detect nephrotic-range proteinuria (≥300 mg/g suggests nephrotic syndrome if accompanied by edema and hyperlipidemia) 5
• Evaluate hydration status clinically, as overhydration dilutes serum albumin concentration 1
• Review comorbidities including diabetes, cardiovascular disease, liver disease, and chronic kidney disease 5, 1
• Check for metabolic acidosis which contributes to hypoalbuminemia and can be corrected with bicarbonate supplementation 5

Context-Specific Considerations

For dialysis patients, albumin must be evaluated alongside peritoneal transport type, delivered dialysis dose (Kt/Vurea), and residual kidney function 5

For surgical patients, albumin <3.0 g/dL indicates significantly increased risk of postoperative complications including infections and poor wound healing 2

Treatment Algorithm

Step 1: Address Underlying Inflammation

Treating active inflammation is the priority, as it is often a more powerful predictor of poor outcomes than low albumin itself 2

• Identify and treat infections, inflammatory conditions, or other catabolic illnesses 5, 1
• Consider that inflammation causes the same changes in serum protein levels as protein-energy malnutrition, even with adequate intake 5

Step 2: Optimize Nutrition

Protein intake targets:

• Hemodialysis patients: 1.2 g/kg/day minimum 2
• Peritoneal dialysis patients: 1.2-1.3 g/kg/day due to dialysate protein losses 5, 2
• Acutely ill or hospitalized patients: 1.2-1.3 g/kg/day minimum 2

Caloric intake targets:

• Patients <60 years: 35 kcal/kg/day 2
• Patients ≥60 years: 30-35 kcal/kg/day 2
• Energy intake <188 kcal/day is associated with negative nitrogen balance in dialysis patients 2

Nutritional monitoring:

• Involve renal dietitian for frequent monitoring 5
• Target normalized protein nitrogen appearance (nPNA) ≥0.9 g/kg/day in dialysis patients 5, 1
• Use Subjective Global Assessment (SGA) rather than albumin alone to assess nutritional status 1

Step 3: Correct Fluid Overload

• Hemodilution from excess fluid decreases serum albumin concentration without true albumin depletion 1
• Optimize volume status through appropriate ultrafiltration in dialysis patients or diuretic therapy in non-dialysis patients 5
• Do NOT use albumin infusion in conjunction with diuretics for removal of extravascular fluid 2

Step 4: Minimize External Protein Losses

• Treat proteinuria with ACE inhibitors or ARBs when appropriate 1
• In peritoneal dialysis patients, consider adjusting dialysis prescription to reduce peritoneal protein losses 1

Step 5: Maintain Adequate Dialysis (for ESRD patients)

• Maintain Kt/Vurea at or above recommended levels (minimum total Kt/Vurea of 1.7 for peritoneal dialysis) 5
• Adequate clearances support but do not independently improve albumin levels 5

Step 6: Correct Metabolic Acidosis

• Oral bicarbonate replacement in dialysis patients with acidosis improves Subjective Global Assessment scores and decreases anorexia 5

Albumin Infusion: When and When Not

DO NOT Use Albumin Infusion For:

• First-line volume replacement in critically ill patients (excluding specific liver disease scenarios) 2, 6
• Simply raising serum albumin levels in hypoalbuminemia—this does not improve survival or reduce morbidity 2, 3, 7
• Volume replacement in conjunction with diuretics for edema mobilization 2
• Preterm neonates with respiratory distress and low albumin 2
• Intradialytic hypotension prevention or treatment 2
• Pediatric cardiovascular surgery 2
• Nutritional purposes 6

DO Use Albumin Infusion For:

Liver disease with strong evidence:

• Large-volume paracentesis (>5L): 8 g albumin per liter of ascites removed to prevent post-paracentesis circulatory dysfunction 2, 6, 8
• Spontaneous bacterial peritonitis: 1.5 g/kg on day 1 and 1.0 g/kg on day 3 (reduces acute kidney injury and mortality, especially if bilirubin >4 mg/dL or creatinine >1.0 mg/dL) 2, 6, 8
• Hepatorenal syndrome (Stage 2-3 AKI in cirrhosis): 1 g/kg daily for 2 consecutive days after withdrawing diuretics 2, 6

Weaker evidence (consider as second-line):

• Fluid replacement in plasmapheresis 6
• Severe burns, toxic epidermal necrolysis (as adjunct to crystalloids) 6
• Ovarian hyperstimulation syndrome 6

Cost consideration: Albumin is expensive (approximately $130/25g USD) with potential adverse effects including fluid overload, hypotension, anaphylaxis, and hemodilution requiring RBC transfusion 2

Monitoring Strategy

Frequency

• Dialysis patients: Monitor serum albumin at least every 4 months 5, 1, 9
• Diabetes patients: Annual screening starting 5 years after type 1 diabetes diagnosis, or at diagnosis for type 2 diabetes 5, 9
• More frequent monitoring during acute illness or when albumin is declining 1

Target Levels

• Dialysis patients: Target predialysis or stabilized serum albumin ≥4.0 g/dL (using bromcresol green method) 5, 2
• General principle: The highest albumin level possible should be the goal for each patient 5
• Trend matters: A decreasing albumin of 0.1 g/dL/month from baseline 4.0 to 3.7 g/dL may indicate higher risk than stable 3.7 g/dL 5

Interpretation

• Use local laboratory standards as normal ranges vary by methodology 5
• Evaluate albumin in context of overall clinical status including comorbidities, inflammatory markers, and fluid status 5, 1
• A stable or rising albumin value suggests the patient is anabolic and increasing protein stores 5, 9

Prognostic Significance

The mortality and morbidity risks are substantial:

• Death risk increases 6% for every 0.1 g/dL decrease in serum albumin in dialysis patients 1
• Each 0.1 g/dL difference associates with 5% change in hospitalization days 1
• Technique failure risk increases 5% for every 0.1 g/dL decrease in peritoneal dialysis patients 1
• Meta-analysis shows 1.0 g/dL decrease increases morbidity odds by 89% and mortality by 137% 2

However, the cause of hypoalbuminemia—rather than low albumin levels specifically—is responsible for morbidity and mortality 3, 7