Serum anion gap revisited: a verified reference interval for contemporary use

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.

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

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 AG_K by [Na⁺ ] + [K⁺ ] - [Cl^- ] - [HCO₃ ^- ]. The reference interval was determined at 2.5th-97.5th percentiles. Analysis was further undertaken for a subcohort of 156 individuals with no suboptimal health indicators.

Median age was 35 years, body mass index 23.4 kg/m² and the glomerular filtration rate was 106 mL/min/1.73 m² . 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 AG_K was 17.7 mmol/L and reference interval was 14.6-22.5 mmol/L.

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.