What are the causes of hypoalbuminemia?

From the Guidelines

Hypoalbuminemia is primarily caused by inflammation, which decreases albumin production, and other conditions such as liver disease, kidney disorders, malnutrition, and protein-losing enteropathies, which either decrease albumin production, increase albumin loss, or cause albumin redistribution in the body. The main causes of hypoalbuminemia include:

• Liver disease (such as cirrhosis, hepatitis, or alcoholic liver disease), which impairs albumin synthesis since the liver is the primary site of production 1
• Kidney disorders like nephrotic syndrome or chronic kidney disease, which lead to excessive albumin loss through the urine
• Malnutrition and protein-deficient diets, which reduce the availability of amino acids needed for albumin synthesis
• Inflammatory states and critical illness, which decrease albumin production through the acute phase response, where the liver prioritizes making other proteins instead of albumin 1
• Protein-losing enteropathies such as inflammatory bowel disease or celiac disease, which cause albumin loss through the gastrointestinal tract
• Burns and other extensive skin injuries, which can result in significant albumin loss through damaged skin
• Pregnancy and hemodilution from excessive IV fluids, which can cause relative hypoalbuminemia due to increased plasma volume Identifying the underlying cause is essential for proper management, as treatment should target the specific mechanism responsible for the low albumin levels rather than just supplementing albumin 1. According to the most recent study, inflammation is a key factor in the development of hypoalbuminemia, and albumin levels should be used in the context of the inflammatory nature of the underlying condition to identify patients at risk of poor outcomes 1.

From the Research

Causes of Hypoalbuminemia

• Hypoalbuminemia can be associated with several different diseases, including cirrhosis, malnutrition, nephrotic syndrome, and sepsis 2
• In patients with heart failure, hypoalbuminemia is thought to result mainly from malnutrition, inflammation, and cachexia, with other causal factors including hemodilution, liver dysfunction, protein-losing enteropathy, increased transcapillary escape rate, and nephrotic syndrome 3
• The underlying conditions that cause hypoalbuminemia, including protein energy malnutrition, crystalloid overload, inflammation, and liver dysfunction, are themselves risk factors for morbidity and mortality 4
• Inflammation increases capillary permeability and escape of serum albumin, leading to expansion of interstitial space and increasing the distribution volume of albumin, resulting in hypoalbuminemia despite increased fractional synthesis rates in plasma 5

Clinical Significance of Hypoalbuminemia

• Hypoalbuminemia has a strong predictive value on mortality and morbidity, regardless of its cause 2
• Hypoalbuminemia has emerged as an independent predictor of incident heart failure in end-stage renal disease and elderly patients 3
• The presence of hypoalbuminemia in patients with heart failure may have potential therapeutic consequences in clinical practice, including the need for removal of subclinical excess of fluid and renutrition 3
• Hypoalbuminemia results from and reflects the inflammatory state, which interferes with adequate responses to events like surgery or chemotherapy, and is associated with poor quality of life and reduced longevity 5

Management of Hypoalbuminemia

• Treatment of hypoalbuminemia should be based on correcting the underlying causes, such as malnutrition, inflammation, and liver dysfunction, rather than infusion of albumin 4, 5
• Management of hypoalbuminemia should focus on correcting the causes of ongoing inflammation, rather than infusion of albumin 5
• Nutrition support cannot fully prevent, but slows down, the chain of events leading to hypoalbuminemia, especially when combined with physical exercise 5