The use and misuse of serum albumin as a nutritional marker in kidney disease.

Nutritional status refers to the composite quantitative and qualitative assessment of visceral and somatic (muscle) protein stores and energy balance (1,2). Evaluating nutritional status is a critical component of physiologic health and fundamental to identifying protein-energy wasting (PEW), a condition highly prevalent and strongly correlated with increased morbidity and mortality in patients with kidney disease (3). Improved recognition of this common condition and effective interventions remain the holy grail of nutritional management of patients with kidney disease, especially those on maintenance dialysis. Assessment of protein and energy nutritional status is a broad and complex topic. A clinically meaningful assessment of nutritional status should be able to identify and risk stratify patientswith PEW,distinguishing the causes and consequences of both PEW and the underlying disease states that lead to PEW, and finally determine whether there is a possibility of benefit from nutritional interventions (4). Therefore, no single parameter is likely to adequately phenotype this comorbid state, and a comprehensive assessment of protein and energy nutritional status requires several different measurements (5). Despite the obvious need for multiple markers, clinicians and researchers have continuously searched for a single marker that would fulfill all the requirements mentioned. Among these markers, serum albumin has been, by far, the most extensively studied serum protein in patients with advanced kidney disease on maintenance dialysis. Serum albumin robustly associates with death and hospitalization, is easily and reproducibly measured, and responds to appropriate interventions (6). Despite these advantages, serum albumin is also one the most highly criticized nutritional markers (7). In this issue of CJASN, Gama-Axelsson et al. (8) report their findings regarding the predictive value of serum albumin as a nutritional marker in a large and well-phenotyped cohort of incident and prevalent maintenance dialysis patients. Their results show that serum albumin was significantly correlated with diabetes mellitus (DM), subjective global assessment (SGA) score .1, indicative of abnormal nutritional status, and urinary albumin excretion in incident dialysis patients. In prevalent dialysis patients, serum albumin was associated with age, C-reactive protein, DM, and SGA .1. They further go on to examine the diagnostic value of serum albumin as a nutritional marker using receiver operating curve (ROC) analysis using SGA, handgrip strength, lean body mass (LBM), and bodymass index (BMI) as gold standards. In these analyses, addition of serum albumin to a standard model including clinical and demographic variables had no appreciable impact for explaining the variability in SGA, handgrip strength, LBM, and BMI. Based on these findings, the investigators conclude that serum albumin correlates poorly with several markers of nutritional status, and thus its value as a reliable marker of nutritional status in ESRD patients is limited. This particular study has multiple strengths including but not limited to a large patient cohort, detailed nutritional and clinical phenotyping, and thorough analysis. The study also has important clinical and research implications. Most importantly, these data, along with other published studies, should guide clinicians and researchers on how to avoid misuse of serum albumin as a nutritional marker in incident and prevalent maintenance dialysis patients. For example, serum albumin has limited diagnostic ability for assessment of body composition, i.e., LBM and fat mass content, and physical functioning because it does not explain the variability in LBM, BMI, or hand grip strength. Similarly, serum albumin had little diagnostic value in identifying poor nutritional status by SGA in this study, which is largely based on the subjective assessment of body composition. Whereas this might seem discouraging, it is important to remember that overall nutritional status is a reflection of both visceral protein concentrations and somatic protein stores, and biomarkers reflecting the status of each compartment are not always tightly correlated. As a result, some of these findings might be anticipated, because serum albumin is a visceral protein, and body composition reflects somatic protein stores. Further, under physiologic stress, such as inflammation, these two compartments often have competing roles with visceral protein production often increasing at the expense of breakdown of somatic proteins, the latter to provide substrate for hepatic protein synthesis (9). Therefore, attempting to use a biomarker (i.e., serum albumin) alone to assess a distinct nutritional compartment without a direct biologic link may misdiagnose this condition of that Division of Nephrology, Department of Medicine, Vanderbilt School of Medicine, Nashville, Tennessee