Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements

Abstract

Serum albumin concentration (CP) is a remarkably strong prognostic indicator of morbidity and mortality in both sick and seemingly healthy subjects. Surprisingly, the specifics of the pathophysiology underlying the relationship between CP and ill-health are poorly understood. This review provides a summary that is not previously available in the literature, concerning how synthesis, catabolism, and renal and gastrointestinal clearance of albumin interact to bring about albumin homeostasis, with a focus on the clinical factors that influence this homeostasis. In normal humans, the albumin turnover time of about 25 days reflects a liver albumin synthesis rate of about 10.5 g/day balanced by renal (≈6%), gastrointestinal (≈10%), and catabolic (≈84%) clearances. The acute development of hypoalbuminemia with sepsis or trauma results from increased albumin capillary permeability leading to redistribution of albumin from the vascular to interstitial space. The best understood mechanism of chronic hypoalbuminemia is the decreased albumin synthesis observed in liver disease. Decreased albumin production also accounts for hypoalbuminemia observed with a low-protein and normal caloric diet. However, a calorie- and protein-deficient diet does not reduce albumin synthesis and is not associated with hypoalbuminemia, and CP is not a useful marker of malnutrition. In most disease states other than liver disease, albumin synthesis is normal or increased, and hypoalbuminemia reflects an enhanced rate of albumin turnover resulting either from an increased rate of catabolism (a poorly understood phenomenon) or enhanced loss of albumin into the urine (nephrosis) or intestine (protein-losing enteropathy). The latter may occur with subtle intestinal pathology and hence may be more prevalent than commonly appreciated. Clinically, reduced CP appears to be a result rather than a cause of ill-health, and therapy designed to increase CP has limited benefit. The ubiquitous occurrence of hypoalbuminemia in disease states limits the diagnostic utility of the CP measurement.

Hepatic FcRn regulates albumin homeostasis and susceptibility to liver injury

“…The latter possibility is likely, in view of the protection observed in therapeutic protocols wherein albumin-FcRn blockade is initiated after APAP exposure, at a time when significant APAP metabolism has already occurred (52). In accordance with human and mouse studies in which hypoalbuminemia results in an increased rate of albumin synthesis (20,53), we detected greater intracellular albumin content in FcRn-deficient hepatocytes and upon antibody-mediated albumin-FcRn blockade. Given the antioxidant capacities of albumin, its accumulation thus can potentially provide additional buffering capacities against oxidative stress and mitochondrial injury during APAP overdose, which involves JNK-dependent, ROS-mediated injury (41).…”

“…This promotion of degradation raises the question whether inducing albumin deficiency through pharmacologic blockade would be beneficial. An accumulating body of evidence illustrates a potential detrimental effect of hypoalbuminemia on health (53,54). At present, no individuals with FcRn-specific deficiency have been described.…”

Associations between serum albumin and serious non-AIDS events among people living with HIV

“…Although low sAlb is commonly regarded as a marker of nutritional status, it is poorly associated with other measures of nutritional status in the general population and in PLWH [8,9]. Other causes of low sAlb may include liver disease (decreased synthesis), enhanced turnover resulting from either increased catabolism or enhanced loss of albumin into the urine or intestine [10], or trans-capillary loss due to increased vascular permeability [11]. The acute phase response, of which interleukin (IL)-6 is a potent inducer, to infectious conditions, neoplastic growth, or immunological disorders, is also associated with inhibition of liver protein synthesis in animal studies [12].…”

Increase in albumin by daclatasvir/asunaprevir therapy is correlated with decrease in aspartate transaminase

“…[17] Since only 20-30% of hepatocytes are committed to the production of albumin in healthy subjects, liver has a large functional reserve to increase the synthesis of albumin by 3−4 times. In cirrhosis, liver has lost this capacity.…”