The mean levels of AG were 12.08 (standard error (SE) 0.15), 1.20 (SE 0.15), and 5.45 (SE 0.16) mEq/L for the traditional, albumin-adjusted, and full AG, respectively. The AG was calculated in the traditional manner (traditional), after adjustment for serum albumin (albumin-adjusted), and after adjustment for serum albumin and other electrolytes (full) (depicted graphically in Figure 1). We tested these hypotheses using data from participants in the National Health and Nutrition Examination Survey (NHANES) 1999–2004. We hypothesized that after accounting for changes in albumin and other electrolytes: (1) higher levels of AG would be present in persons with relatively preserved glomerular filtration rate (GFR), and (2) higher AG would be associated with increased risk of mortality in individuals without advanced kidney disease. 7– 9 Calculation of the AG after accounting for electrolyte measurements that are not traditionally included, in addition to the serum albumin, could also yield a measurement with greater specificity for the accumulation of organic anions.
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Such changes may be of prognostic significance as higher levels of the AG have been associated with hypertension, insulin resistance, and low cardiorespiratory fitness in nationally representative populations largely free of advanced kidney disease.
4 Therefore, the AG may increase earlier in the course of CKD than has been previously recognized. 4, 5 However, variations in the serum albumin concentration affect the AG, 6 and these studies have not accounted for the hypoalbuminemia that commonly accompanies progressive kidney disease. 1– 3 Studies of the general population have supported this view. Previous studies in persons with CKD have demonstrated an increase in the AG only with relatively advanced kidney disease.
Whether changes in the AG occur earlier in the course of chronic kidney disease (CKD) has been little explored. It is well known that uremia causes an increase in the serum anion gap (AG) due to the accumulation of a variety of solutes. Further study is needed to identify the unmeasured anions and to determine their physiologic significance. Thus, higher levels of anion gap are present in individuals with less advanced kidney disease than previously recognized, and are associated with increased risk of mortality. After adjustment for additional covariates including body-mass index and comorbidities, higher levels of the albumin-adjusted and full anion gap were associated with mortality (relative hazard for highest compared to the lowest quartile were 1.62 and 1.64, respectively). Higher levels of each anion gap were associated with an increased risk of all-cause mortality after adjustment for age, gender, race/ethnicity, and eGFR. A significant elevation in the traditional anion gap was seen only with an estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73m 2, whereas increases in the albumin-adjusted and full anion gap were found with eGFRs less than 60 or 90mL/min/1.73m 2, respectively. 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 anion gap using the traditional method, or one that was albumin-adjusted, as well as a full anion gap reflecting other electrolytes. Here we investigated whether different measures of the anion gap, as a marker of kidney function, are associated with mortality. It is well known that uremia causes an increase in the serum anion gap however, whether changes in the anion gap occur earlier in the course of chronic kidney disease is not known.
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