Hypoalbuminaemia

Hypoalbuminaemia is a serum albumin concentration under 35 g/L (reference range 35 to 50 g/L). It results from reduced synthesis, increased loss, redistribution, or dilution, and it is a marker of illness severity and poor prognosis rather than a disease. Low albumin reduces plasma oncotic pressure (causing oedema and effusions) and lowers total (but not free) calcium and bound drug levels.

• Reduced synthesis: chronic liver disease and cirrhosis, malnutrition and protein energy malnutrition (kwashiorkor), malabsorption, chronic inflammation and sepsis (albumin is a negative acute phase reactant), and critical illness.
• Increased loss: nephrotic syndrome (urinary loss over 3.5 g/24 h), protein losing enteropathy (inflammatory bowel disease, coeliac disease, intestinal lymphangiectasia, heart failure, intestinal TB), burns, exudative skin disease, haemorrhage, peritoneal dialysis, and large effusions.
• Redistribution and dilution: sepsis with capillary leak, third spacing, pregnancy (physiological fall), fluid overload, heart failure, and intravenous fluid administration.
• Increased catabolism: cancer cachexia, thyrotoxicosis, trauma, and corticosteroids.
• Rare: analbuminaemia.
• Plasma half life of albumin is about 20 days, so acute changes in synthesis take weeks to appear.

• Oedema (pitting leg oedema, periorbital swelling, sacral oedema), ascites, pleural effusions, weight gain, and fatigue.
• Features of the cause: jaundice and spider naevi (liver disease), frothy urine and hypertension (nephrotic syndrome), diarrhoea and weight loss (enteropathy), muscle wasting and hair changes (malnutrition), fever and illness (sepsis), heart failure signs, skin lesions or burns.
• Complications: impaired wound healing, infections, delayed drug clearance (high risk with warfarin, phenytoin, and others), venous thromboembolism in nephrotic syndrome, and poor prognosis in critical illness.
• History: diet, alcohol, diarrhoea, urinary symptoms, chronic diseases, medicines, and HIV, hepatitis and TB risk.
• Examination: nutritional status (body mass index, mid-upper arm circumference), oedema, ascites, jaundice, blood pressure, heart and lung signs, abdominal organs, and skin.

• Repeat serum albumin with total protein, globulin (total protein minus albumin), and liver function; low albumin with high globulin suggests chronic inflammation, liver disease, or paraprotein; low albumin with low globulin suggests malnutrition, protein loss, or dilution.
• Urine: dipstick, urine protein creatinine ratio (over 300 mg/mmol, or 3 g/day, in nephrotic syndrome), 24 hour protein, and urine microscopy.
• Liver tests: ALT, AST, bilirubin, alkaline phosphatase, gamma glutamyl transferase, INR (prolonged in synthetic failure), abdominal ultrasound.
• Renal function, electrolytes, lipids (high in nephrotic syndrome), glucose, thyroid function, CRP, FBC, ESR, HIV, hepatitis B and C serology.
• Nutritional assessment: dietary history, weight loss, prealbumin, vitamin and mineral levels.
• Gastrointestinal protein loss: faecal alpha-1 antitrypsin clearance, coeliac serology, faecal calprotectin, endoscopy and imaging.
• Imaging: echocardiogram for heart failure, chest X-ray.
• Renal biopsy for adults with nephrotic syndrome; paraprotein tests (serum protein electrophoresis, serum free light chains) for amyloidosis.
• Interpret calcium: corrected calcium (measured calcium plus 0.02 x (40 minus albumin in g/L)) in mmol/L, or ionised calcium.

Treat the cause (primary strategy)

• Nephrotic syndrome: treat the cause; loop diuretic (furosemide 40 to 80 mg daily orally, titrated to weight loss of 0.5 to 1 kg daily), ACE inhibitor (ramipril 2.5 mg increasing to 10 mg) or angiotensin receptor blocker for proteinuria, salt restriction under 2 g sodium daily, statin, anticoagulation when albumin is under 20 to 25 g/L with other risk factors (apixaban 5 mg twice daily or warfarin), and specialist immunosuppression (prednisolone 1 mg/kg daily in minimal change disease).
• Cirrhosis: abstinence from alcohol, sodium restriction (under 2 g daily), spironolactone 100 mg increasing to 400 mg daily with furosemide 40 to 160 mg daily for ascites, protein intake 1.2 to 1.5 g/kg/day with late evening snack, treat the cause (hepatitis antivirals), and large volume paracentesis with albumin 8 g per litre of ascites removed when more than 5 litres is drained.
• Protein losing enteropathy: treat the cause (inflammatory bowel disease, coeliac disease, infection, heart failure); medium chain triglyceride diet in lymphangiectasia.
• Malnutrition: oral nutritional support and a high protein, high energy diet (protein 1.2 to 1.5 g/kg/day, energy 30 to 35 kcal/kg/day), micronutrient replacement, refeeding precautions (thiamine 100 mg daily, check phosphate, potassium, and magnesium), and nasogastric or parenteral feeding when needed.
• Sepsis and inflammation: treat the infection or inflammatory disease; albumin will recover.
• Heart failure: diuretics and usual heart failure drugs.
• Burns and skin disease: protein and fluid replacement, wound care.

Albumin infusion (limited, specific indications)

• Large volume paracentesis (over 5 litres): 20 percent albumin 8 g per litre removed; spontaneous bacterial peritonitis: albumin 1.5 g/kg on day 1 and 1 g/kg on day 3 with antibiotics; hepatorenal syndrome: albumin 1 g/kg (maximum 100 g) on day 1 then 20 to 40 g daily with terlipressin; refractory oedema with hypovolaemia in nephrotic syndrome (20 percent albumin 0.5 to 1 g/kg with furosemide).
• No benefit from albumin infusion solely to correct a low serum level in hospital patients; avoid routine use for hypoalbuminaemia, nutrition, or wound healing.

Drug adjustment

• Reduce doses or monitor free levels of highly protein bound drugs: phenytoin (use free level or corrected concentration), warfarin (INR), valproate, diazepam, and others.
• Use corrected calcium or ionised calcium.

Follow up

• Monitor albumin, weight, oedema, and urine protein; repeat albumin every 1 to 4 weeks during treatment; nutritional review at each visit; specialist referral for nephrotic syndrome, cirrhosis, and unexplained persistent hypoalbuminaemia.