Sodium-chloride difference is not strongly correlated with base excess in chronic kidney disease: an anion gap problem

Introduction: The prevalence of metabolic acidosis is high in patients with chronic kidney disease (CKD). For the diagnosis, a blood gas analysis is necessary, but not always available. The aim of the study was to evaluate the base excess (BE) of the sodium-chloride difference (BE_Na-Cl = Na⁺-Cl^--34 mmol/l) as a screening parameter for hyperchloremic metabolic acidosis.

Methods and statistical analysis: We retrospectively performed acid-base analyses of 168 non-dialysed patients with CKD according to the physiologic and to the Stewart's approach. We performed linear regression analysis, Bland-Altman plot and receiver operating characteristics (ROC) analysis of BE_Na-Cl and BE to evaluate the accuracy of BE_Na-Cl predicting the BE. We further investigated possible confounding factors.

Results: The corrected R² for the correlation of BE_Na-Cl and BE was 0.60 (p < 0.001). The Bland-Altman plot showed a good overall agreement. The bias was negligible, but the 95%-limits of agreement showed a wide interval (10.4 mmol/l). For BE ≤ 2 mmol/l, the ROC analysis yielded an AUC of 0.89 and moderate sensitivity (0.75) and specificity (0.86) for the optimal BE_Na-Cl threshold (≤ 2 mmol/l). Subgroup analysis showed similar results. The main factor for the imprecision of BE_Na-Cl predicting the BE across all stages of CKD is the variability of the serum anion gap (SAG).

Conclusions: The BE_Na-Cl is not an adequate parameter for screening of hyperchloremic acidosis because of the high variability of the SAG. Only, if the BE_Na-Cl is ≤ 5 mmol/l, a hyperchloremic acidosis should be suspected. Therefore, a complete blood gas analysis is necessary for the correct diagnosis of acid-base disorders in patients with chronic kidney disease.