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The Serum Anion Gap Revisited: A Verified Reference Interval for Contemporary Use

Intern Med J. 2021 May 24. doi: 10.1111/imj.15396. Online ahead of print.

ABSTRACT

BACKGROUND: The anion gap (AG) is often used to evaluate acid-base disorders. The reference interval for normal AG is used to differentiate between raised (gap) or normal AG (non-gap) acidosis. Historically accepted AG values may not be valid with the evolution of modern analytical techniques and the reference interval requires revalidation.

AIMS: To determine the reference interval for AG based on current laboratory techniques.

METHODS: During a health-screening exercise, 284 participants with no major illnesses volunteered surplus blood for analysis. The samples were tested in an internationally-accredited clinical laboratory. AG was calculated by (Na+ ) – (Cl ) – (HCO3 ) and AGK by (Na+ ) + (K+ ) – (Cl ) – (HCO3 ). The reference interval was determined at 2.5th-97.5th percentiles. Analysis was further undertaken for a sub-cohort of 156 individuals with no sub-optimal health indicators.

RESULTS: Median age was 35 years, BMI 23.4 kg/m2 and glomerular filtration rate 106 mL/min/1.73m2 . Median AG was 13 mmol/L and the reference interval for normal AG is 10-18 mmol/L with a 99% level of confidence. Statistically significant differences in AG were detected for sex, race, obesity and serum albumin but the difference was 1 mmol/L between subgroups. The reference interval was the same for the sub-cohort of 156 individuals. Median AGK was 17.7 mmol/L and reference interval was 14.6-22.5 mmol/L.

CONCLUSIONS: The AG reference interval of 10-18 mmol/L is valid for laboratories with similar reference intervals for electrolytes. Lower values expected with current laboratory techniques were not observed. The median AG of 13 mmol/L may be used to differentiate gap acidosis, non-gap acidosis or mixed acid-base disorders. This article is protected by copyright. All rights reserved.

PMID:34028972 | DOI:10.1111/imj.15396

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