The elevation of the anion gap in steady state chronic kidney disease may be less prominent than generally accepted

Background A presumed cause of metabolic acidosis in chronic kidney disease (CKD) is accumulation of unmeasured anions, leading to a high anion gap (AG). In patients with CKD with a high AG, only minor increases are expected. The aim of this study is to evaluate the magnitude of the AG in documented steady state CKD to examine the effect of CKD on a high-AG metabolic acidosis (HAGMA). Methods In this cross-sectional study the AG, bicarbonate, and chloride were evaluated in 1045 blood and urine samples of 501 patients with steady state CKD in the outpatient clinic. The influence of phosphate, albumin and potassium on the AG were evaluated. Results The mean AG increased from 8.8 mEq/l (+/- 1.57) in CKD stage 1 to 11.2 mEq/l (+/- 2.22) in CKD stage 5 (P < 0.001). Correction for albumin or phosphate did not influence the magnitude of the AG. Correction for potassium did alter the prevalence of HAGMA, but not the severity. [HCO3-] decreased between CKD stages 1 and 5 by 5.1 mEq/l. The [Cl-] increased by 2.6 mEq/l between CKD stages 1 and 5. Conclusions The elevation of the AG in patients with steady state CKD is limited and less pronounced than the decrease in [HCO3-]. Normal AG metabolic acidosis seems to be more important in CKD than HAGMA. The CKD stage and the magnitude of the AG should be taken into account when evaluating a patient with HAGMA. This study suggests that an AG >15 mEq/l is rarely due to renal failure alone. Lay Summary CKD is one of several diseases in which blood can become acidic. The acidification of blood in CKD is partially due to accumulation of acids that are normally excreted by the kidneys. These negatively charged acids increase the difference in the concentrations of the main positively charged electrolyte (sodium) and negatively charged electrolytes (bicarbonate and chloride), called the AG. An increase in the AG can have different causes. The magnitude of the AG depends on the disease, but is often not accounted for when evaluating a high AG. It is generally only considered 'elevated or not elevated'. We found that the increase of the AG in different severities of renal failure is very limited. This means that it is important to account for the magnitude of the AG and the severity of the CKD. before attributing it to the renal insufficiency alone. When disregarding these two aspects, one could miss other possible causes of the increased AG.

Automated summary

The increase of Anion Gap in patients with chronic kidney disease (CKD) is limited and less pronounced than the decrease in HCO3-. The severity of CKD and the magnitude of the Anion Gap should be taken into account when evaluating metabolic acidosis.