Higher anion gap linked to increased mortality

A higher serum anion gap early in the course of kidney disease is associated with significantly increased mortality, reports a study in Kidney International.

Using data on 11,957 adults from the National Health and Nutrition Examination Survey 1999 to 2004, the researchers analyzed the relation between the anion gap, as a marker of kidney function, and mortality. Laboratory data were used to calculate the anion gap by the traditional method, with adjustment for albumin, or the full anion gap reflecting other electrolytes. The frequency of elevated anion gap relative to GFR was analyzed, including its association with mortality risk in study participants without advanced kidney disease.

The “traditional” anion gap was elevated only in participants with estimated GFR less than 45 mL/min/1.73 m2. By contrast, significant elevations were found for the albumin-adjusted anion gap in patients with GFR values less than 60 mL/min/1.73 m2, and for the full anion gap at GFR values of 90 mL/min/1.73 m2.

With adjustment for body mass index, comorbidities, and other covariates, higher anion gap levels were associated with increased mortality. For the highest versus lowest quartiles, the relative hazard ratios were 1.62 for the albumin-adjusted anion gap and 1.64 for the full anion gap.

Uremia is associated with an increased serum anion gap, but it has been unclear whether elevations can occur earlier in the course of kidney disease. This study presents evidence that higher anion gaps can also occur with less advanced kidney disease and are associated with increased mortality. The authors call for further studies “to identify the unmeasured anions and to determine their physiological significance.” [Abramowitz MK, et al. The serum anion gap is altered in early kidney disease and associates with mortality. Kidney Int 2012; 82:701–709].