TY - JOUR
T1 - The serum anion gap is altered in early kidney disease and associates with mortality
AU - Abramowitz, Matthew K.
AU - Hostetter, Thomas H.
AU - Melamed, Michal L.
N1 - Funding Information:
This research was supported by National Institutes of Health (NIH) grants K23DK078774 to Dr Melamed; R21DK077326, R01DK087783, and RO1DK080123 to Dr Hostetter; and CTSA grants UL1RR025750, KL2RR025749, and TL1RR025748 from the National Center for Research Resources, a component of the NIH.
PY - 2012/9/2
Y1 - 2012/9/2
N2 - 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/minper1.73 m2, whereas increases in the albumin-adjusted and full AG were found with eGFRs <60 or 90 ml/minper1.73 m2, 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.
AB - 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/minper1.73 m2, whereas increases in the albumin-adjusted and full AG were found with eGFRs <60 or 90 ml/minper1.73 m2, 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.
KW - kidney disease
KW - mortality
KW - uremic toxins
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U2 - 10.1038/ki.2012.196
DO - 10.1038/ki.2012.196
M3 - Article
C2 - 22622500
AN - SCOPUS:84865704621
SN - 0085-2538
VL - 82
SP - 701
EP - 709
JO - Kidney international
JF - Kidney international
IS - 6
ER -