Influence of hypoalbuminemia or hyperalbuminemia on the serum anion gap

Background: Conflicting data exist as to what extent hypoalbuminemia reduces the anion gap; estimates range from 1.5 to 2.5 mM per g/dL decrease in serum albumin. Methods: We measured serum albumin, total protein, and electrolyte concentrations in 5328 consecutive patients aged 1 month to 102 years. Most patients (3750; 70%) had a normal albumin, but 1158 had hypoalbuminemia (≤3.4 g/dL); 420 had hyperalbuminemia (≥4.7 g/dL). Relationships between serum albumin or total protein and the anion gap were analyzed by linear regression. Results: 309 (27%) hypoalbuminemic patients had a decreased anion gap, and 257 hyperalbuminemic patients (61%) had an increased anion gap. Among the entire group of 5328 patients, there were highly significant correlations between either serum albumin or total protein and the anion gap (P < 0.001). The slope of the regression for albumin versus anion gap was 2.3 mM per g/dL. Using this slope, anion gap could be adjusted for abnormal serum albumin levels: anion gap_adjusted =anion gap + 2.3 (4-albumin). The initial assessment of an anion gap as being increased, normal, or decreased changed in 44% of the patients with hypo- or hyperalbuminemia once anion gap had been adjusted with this formula. Conclusions: Before considering whether a disorder associated with an increased or decreased anion gap is present, the anion gap should be first adjusted for abnormal serum albumin concentrations. Our data suggest that physicians use 2.3 times the change in serum albumin, whereas those of Figge et al suggest 2.5; either approach gives similar results.