Things We Do For No Reason: Prealbumin Testing to Diagnose Malnutrition in the Hospitalized Patient

Prealbumin is synthesized in the liver and released into circulation prior to excretion by the kidneys and gastrointestinal tract. Prealbumin transports thyroxine, triiodothyronine, and holo-retinol binding protein and, as a result, is also known as transthyretin.⁷ It was first proposed as a nutritional marker in 1972 with the publication of a study that showed low levels of prealbumin in 40 children with kwashiorkor that improved with intensive dietary supplementation.⁸ The shorter half-life of prealbumin (2.5 days) as compared with other identified nutritional markers, such as albumin, indicate that it would be suitable for detecting rapid changes in nutritional status.

Prealbumin Is Not Specific

An ideal nutritional marker should be specific enough that changes in this marker reflect changes in nutritional status.⁹ While there are many systemic factors that affect nutritional markers, such as prealbumin (Table 1), the acute phase response triggered by inflammation is the most significant confounder in the acutely ill hospitalized patient.⁹ This response to infection, stress, and malignancy leads to an increase in proinflammatory cytokines, increased liver synthesis of inflammatory proteins, such as C-reactive protein (CRP), and increased vascular permeability. Prealbumin is a negative acute phase reactant that decreases in concentration during the stress response due to slowed synthesis and extravasation.⁹ In a study of 24 patients with severe sepsis and trauma, levels of prealbumin inversely correlated with CRP, a reflection of the stress response, and returned to normal when CRP levels normalized. Neither prealbumin nor CRP, however, correlated with total body protein changes.¹⁰ Unfortunately, many studies supporting the use of prealbumin as a nutritional marker do not address the role of the acute phase response in their results. These studies include the original report on prealbumin in kwashiorkor, a condition known to be associated with a high rate of infectious diseases that can trigger the acute phase response.⁹ A consensus statement from the Academy of Nutrition and Dietetics (AND) and ASPEN noted that prealbumin is an indicator of inflammation and lacks the specificity to diagnose malnutrition.¹¹

Prealbumin Is Not Sensitive

A sensitive laboratory test for malnutrition should allow for detection of malnutrition at an early stage.⁹ However, patients who demonstrate severe malnutrition without a coexisting inflammatory state do not consistently show low levels of prealbumin. In a systematic review of 20 studies in nondiseased malnourished patients, only two studies, both of which assessed patients with anorexia nervosa, had a mean prealbumin below normal (<20 mg/dL), and this finding corresponded to patient populations with mean BMIs less than 12 kg/m². More importantly, normal prealbumin levels were seen in groups of patients with a mean BMI as low as 12.9 kg/m².¹² Analysis by AND found insufficient evidence to support a correlation between prealbumin and weight loss in anorexia nervosa, calorie restricted diets, or starvation.¹³ The data suggest that prealbumin lacks sufficient sensitivity to consistently detect cases of malnutrition easily diagnosed by history and/or physical exam.

Prealbumin Is Not Consistently Responsive to Nutritional Interventions