title: The serum anion gap is altered in early kidney disease and associates with mortality.
abstract: It is well known that uremia causes an increase in the serum anion gap (AG); however, whether changes in the AG occur earlier in the course of chronic kidney disease is not known. Here we investigated whether different measures of the AG, as a marker of kidney function, are associated with mortality. To do this, we analyzed the available laboratory data of 11,957 adults in the National Health and Nutrition Examination Survey 1999-2004 to calculate AG using the traditional method, or one that was albumin-adjusted, as well as a full AG reflecting other electrolytes. A significant elevation in the traditional AG was seen only with an estimated glomerular filtration rate (eGFR) <45 ml/min per 1.73 m(2), whereas increases in the albumin-adjusted and full AG were found with eGFRs <60 or 90 ml/min per 1.73 m(2), respectively. Higher levels of each AG were associated with an increased risk of all-cause mortality after adjustment for age, gender, race/ethnicity, and eGFR. After adjustment for additional covariates including body mass index and comorbidities, higher levels of the albumin-adjusted and full AG were associated with mortality (relative hazard for the highest compared with the lowest quartile were 1.62 and 1.64, respectively). Thus, higher levels of AG are present in individuals with less advanced kidney disease than previously recognized, and are associated with increased risk of mortality. Further study is needed to identify the unmeasured anions and to determine their physiological significance.
authors.affiliation: Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA. matthew.abramowitz@einstein.yu.edu
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Abramowitz
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hostetter
authors.forename: Michal L
authors.initials: ML
authors.lastname: Melamed
mesh_terms: D000136:Acid-Base Equilibrium; D000328:Adult; D000419:Albuminuria / Q000097:blood / Q000401:mortality / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D015897:Comorbidity; D018450:Disease Progression; D004573:Electrolytes / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017711:Nonlinear Dynamics; D009749:Nutrition Surveys; D011379:Prognosis; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000175:diagnosis / Q000401:mortality* / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D012709:Serum Albumin / Q000032:analysis; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D004573:Electrolytes; D012709:Serum Albumin