AlbuminEdit

Albumin is the most abundant protein in human blood plasma, accounting for roughly 60% of the total plasma protein and playing a central role in fluid balance and transport. It is produced predominantly by hepatocytes in the liver and serves as a versatile carrier for a wide range of endogenous and exogenous substances, including bilirubin, free fatty acids, metal ions, hormones, and various drugs. Beyond its transport duties, albumin contributes substantially to colloid osmotic pressure (oncotic pressure) in the vascular system, helping to retain fluid within the bloodstream and supporting overall circulation. Clinically, serum albumin levels are used as a parameter in assessing liver function, nutritional status, and inflammatory states, while preparations of albumin are employed therapeutically as a plasma volume expander and in specific disease contexts.

Biology and biochemistry

Albumin is a single-chain polypeptide of about 585 amino acids, with a native molecular weight of approximately 66.5 kDa. The protein has a distinctive structure formed by three homologous domains (domain I, II, and III), each further subdivided into subdomains. This architecture underpins albumin’s remarkable versatility as a binding partner, enabling it to accommodate a broad spectrum of ligands with high affinity and specificity. Binding sites on albumin include the well-described Sudlow sites I and II, which are principal loci for the attachment of various drugs and endogenous compounds. The albumin molecule is synthesized in the liver from the ALB gene, located on chromosome 4, and is secreted into the bloodstream where it contributes to about a 19–20 day half-life under normal conditions, though this can be influenced by illness and volume status. In the circulation, albumin’s functions extend from maintaining oncotic pressure to serving as a reservoir for essential ligands, buffering pH, and participating in antioxidant defense.

In health, albumin helps maintain intravascular fluid balance, thereby supporting perfusion of tissues and organs. When levels drop (hypoalbuminemia), the risk of edema and hypotension rises, a situation commonly seen in malnutrition, chronic liver disease, nephrotic syndromes, and acute inflammatory states. Albumin’s transport capabilities also influence the pharmacokinetics of many medications, a consideration that is important in clinical pharmacology and in designing treatment regimens.

Medical uses

Diagnostic value

  • Serum albumin concentration is routinely measured as part of liver and nutritional assessments. Low levels can indicate impaired hepatic synthetic function, renal losses, malnutrition, or systemic inflammation, while high levels are less common but may be seen in certain dehydration states or chronic inflammatory conditions.

Therapeutic uses

  • Plasma volume expansion: Albumin solutions are used to expand intravascular volume in selected settings, such as hypovolemia due to acute illness, surgery, burns, or trauma. The choice between albumin and crystalloids for resuscitation is guided by patient condition, cost considerations, and evolving evidence on outcomes.
  • Cirrhosis and ascites: When large-volume paracentesis is performed to relieve ascites, albumin infusion is often used to prevent circulatory dysfunction and renal impairment. Albumin’s osmotic and carrier properties support hemodynamic stability in this context.
  • Other uses: Albumin is employed in certain hypoalbuminemic states where fluid management and ligand transport are clinically beneficial. Its role is typically determined by evidence of benefit in specific indications and by regulatory and formulary guidelines.

Pharmacology and pharmacokinetics

  • Distribution and binding: In the bloodstream, albumin binds a broad array of ligands with high capacity and variable affinity. The binding can influence the distribution, efficacy, and elimination of many drugs, making albumin an important consideration in dose adjustments.
  • Metabolism and clearance: Albumin is primarily catabolized by the reticuloendothelial system and other tissues, with minimal renal excretion under normal conditions. Its turnover is relatively slow, reflecting its role as a stable carrier protein in circulation.
  • Drug interactions: Because albumin binds many pharmaceuticals, changes in albumin concentration can alter free drug levels, potentially affecting efficacy and toxicity. Clinicians monitor this dynamic when managing treatments for patients with liver disease, malnutrition, or critical illness.

Controversies and debates

  • Sepsis and critical care: The clinical value of albumin in fluid resuscitation remains a topic of debate. The prominent SAFE trial compared 4% albumin with normal saline in ICU patients and found no overall mortality difference, highlighting that the choice of resuscitation fluid may be tailored to individual patient characteristics rather than adopting a one-size-fits-all approach. Subsequent analyses suggested potential benefits in subgroups, such as patients with lower serum albumin or specific hemodynamic profiles, but results are not unambiguous. Ongoing debates focus on identifying which patients derive meaningful benefit, the optimal dosing strategies, and the relative cost-effectiveness compared with crystalloids. See also SAFE trial and Surviving Sepsis Campaign.
  • Cost and resource allocation: Albumin is more expensive than many crystalloids, and its use in marginal indications has prompted discussions about health economics, formulary decisions, and the appropriate balance between proven benefit and budgetary constraints. Proponents argue that albumin’s selective, evidence-based use in members of high-risk groups can improve outcomes and reduce downstream costs, while critics emphasize prudent stewardship and the primacy of cost containment in public and private health systems.
  • Evidence synthesis and guidelines: As with many complex therapies, meta-analyses and guidelines continue to evolve. Advocates for a cautious, evidence-based approach stress the need for precise patient stratification and well-designed trials, whereas others argue for broader application in light of mechanistic plausibility and observational signals. The debate often centers on how best to translate physiology into practice without over-promising benefits.

Production, regulation, and supply

  • Source and safety: Therapeutic albumin is a plasma-derived product, collected from screened donors under strict regulatory oversight. Producers emphasize safety testing, viral inactivation methods, and traceability to safeguard patients. The dependence on donor plasma has implications for supply stability and pricing, especially in markets with fluctuating demand.
  • Policy and markets: From a policy perspective, the balance between public funding, private manufacturing, and patient access shapes albumin availability. Efficient procurement, transparent pricing, and evidence-based guidelines are valued by stakeholders who favor market-driven reform, competition, and patient-centered care, while ensuring safety and quality standards.

See also