How to correct hypoalbuminemia (low albumin levels)?

How to Correct Hypoalbuminemia

The primary approach to correcting hypoalbuminemia is to identify and treat the underlying cause—particularly inflammation, malnutrition, or protein loss—rather than simply administering albumin, as recommended by the American College of Physicians. 1

Understanding the Pathophysiology

Hypoalbuminemia is predominantly a marker of inflammation rather than pure nutritional deficiency in most clinical contexts. 2, 1, 3

• Inflammatory cytokines (TNF-α, IL-6) directly downregulate hepatic albumin synthesis, even when protein and caloric intake are adequate 2, 4
• Inflammation increases capillary permeability, causing albumin to leak into the interstitial space and expand its distribution volume 3
• The half-life of albumin shortens during inflammatory states, reducing total albumin mass despite increased fractional synthesis rates 3
• Multiple non-nutritional factors affect serum albumin including age, comorbidities (cardiovascular disease, diabetes), external protein losses (urine, dialysate), and fluid overload 2

Primary Treatment Strategy

Step 1: Address the Underlying Cause

• Treat active inflammation as the priority, since inflammation is often a more powerful predictor of poor outcomes than low albumin itself 2
• Provide adequate nutritional support with protein intake of 1.2-1.3 g/kg body weight/day, especially in malnourished patients 1
• Prevent and treat catabolic illness that drives protein breakdown 1
• Correct fluid overload, as hemodilution from excess fluid decreases serum albumin concentration 2, 1
• Optimize dialysis adequacy (Kt/V urea) in dialysis patients 1
• Minimize external protein losses by treating proteinuria or reducing dialysate losses where possible 2

Step 2: Monitor Response

• Measure serum albumin regularly (at least every 4 months in chronic conditions) 1
• Consider measuring C-reactive protein or other inflammatory markers to distinguish inflammation-driven hypoalbuminemia from pure malnutrition 2, 1
• Target a serum albumin ≥4.0 g/dL (using bromcresol green method) in dialysis patients, or at least the lower limit of normal range 1

When Albumin Infusion IS Indicated

Albumin administration should be reserved for specific clinical scenarios with evidence-based benefit, not for correcting low albumin levels per se. 1

Strong Indications (High-Quality Evidence):

• Large-volume paracentesis (>5L) in cirrhotic patients: Administer 8g albumin per liter of ascites removed to prevent paracentesis-induced circulatory dysfunction 1, 5, 6
• Spontaneous bacterial peritonitis: Albumin infusion is recommended, particularly when serum creatinine is elevated 1, 6
• Hepatorenal syndrome: Part of standard management in liver disease 6
• Hypovolemic shock: Plasbumin-25 is hyperoncotic and expands plasma volume 3-4 times the administered volume by drawing fluid from interstitial spaces 5

Potential Indications (Lower-Quality Evidence):

• Severe burns beyond 24 hours: To maintain plasma albumin around 2.5 ± 0.5 g/dL with oncotic pressure of 20 mmHg 5
• Neonatal hemolytic disease: 1 g/kg body weight given 1 hour prior to exchange transfusion to bind free bilirubin 5
• Cardiopulmonary bypass: To achieve hematocrit of 20% and plasma albumin of 2.5 g/dL during pump prime 5

When Albumin Infusion Is NOT Recommended

The American Thoracic Society and other major guidelines explicitly recommend against albumin in multiple scenarios: 1

• First-line volume replacement in critically ill patients (excluding thermal injuries and ARDS) 1
• Simply to raise serum albumin levels in any patient population 1
• Volume replacement in critically ill patients with thermal injuries or ARDS 1
• In conjunction with diuretics for extravascular fluid removal 1
• Preterm neonates with respiratory distress and low albumin 1
• Prevention or treatment of intradialytic hypotension during kidney replacement therapy 1
• Pediatric patients undergoing cardiovascular surgery 1
• Hyperoncotic albumin targeting >30 g/L in hospitalized patients with decompensated cirrhosis (showed no improvement in infections, kidney dysfunction, or death) 1

Special Populations

Dialysis Patients:

• Ensure adequate nutrition monitored by a renal dietitian 1
• Target normalized protein nitrogen appearance (nPNA) ≥0.9 g/kg/day 1
• Maintain adequate dialysis clearance 1
• In patients with high urea levels, prioritize effective dialysis over albumin administration 1
• Be aware that newer "protein-leaking" or medium cut-off dialyzer membranes increase albumin losses into dialysate 7

Surgical Patients:

• Preoperative albumin <3.0 g/dL is associated with increased surgical complications including infections and poor wound healing 1
• Preoperative nutritional assessment and optimization is recommended when albumin <3.0 g/dL 1
• Correction of nutritional deficiency is recommended when feasible before cardiac surgery (Class IIa recommendation) 1

Steroid-Treated Patients:

• Corticosteroids increase net protein loss and drive catabolism, worsening hypoalbuminemia 1
• Use steroids for the shortest time possible with downward dose titration 1
• Monitor nutritional status in patients requiring long-term steroid therapy 1

Critical Pitfalls to Avoid

• Assuming hypoalbuminemia equals malnutrition: Inflammation is often the primary driver, not nutritional deficiency 2, 1, 3
• Failing to recognize albumin as a negative acute-phase reactant: It decreases during inflammation regardless of nutritional status 2, 1
• Administering albumin without addressing the underlying cause: Simply giving albumin to critically ill hypoalbuminemic patients has not been shown to improve survival or reduce morbidity 3, 4
• Using albumin as a nutritional supplement: Long-term albumin administration should not be considered a source of nutrition 5

Risks of Albumin Infusion

When albumin is administered, be aware of potential complications: 1

• Fluid overload and pulmonary edema (especially if infusion rate exceeds 2 mL/min in hypoproteinemic patients with normal blood volumes) 5
• Hypotension
• Hemodilution requiring RBC transfusion
• Anaphylaxis
• Peripheral gangrene
• High cost (approximately $130 per 25g) 1

Dosing When Albumin Is Indicated

• Large-volume paracentesis: 8g albumin per liter of ascites removed 1, 5
• Hypovolemic shock: Total dose should not exceed 2 g/kg body weight in absence of active bleeding 5
• Hypoproteinemia (when symptomatic treatment needed): Adults 50-75g daily, children 25g daily, at infusion rate not exceeding 2 mL/min 5
• Burns: Maintain plasma albumin around 2.5 ± 0.5 g/dL 5
• Congenital nephrotic syndrome with symptomatic hypovolemia: 1-4 g/kg daily based on clinical indicators 1