Association of serum sodium minus chloride level at initiation of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and hyperkalemia in patients with CKD: a case control study

Abstract

Abstract Background Angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) exert a renoprotective effect on patients with chronic kidney disease (CKD). Despite their benefit, one of their side effects is hyperkalemia, and it is one of the most common reasons for discontinuation of these drugs. Hyperchloremic metabolic acidosis is a known risk factor for hyperkalemia in patients with CKD. However, whether it is a risk factor for hyperkalemia after initiating ACE-I or ARB remains unclear. Methods In a previous study, serum sodium minus chloride level ([Na+) − (Cl−]) was identified as useful for diagnosing metabolic acidosis. To estimate the baseline acid–base status, we determined for the cutoff value of [Na+] − [Cl−] that correlates with [HCO3−] below 24 mEq/L in patients with CKD. We then investigated whether this cutoff value was associated with hyperkalemia (serum potassium level ≥ 5.0 mEq/L) after initiating ACE-I or ARB in patients with CKD. Results In the investigation of the cutoff value of [Na+] − [Cl−], 612 patients were examined, and [Na+] − [Cl−] showed a good correlation with [HCO3−] (r = 0.67, p < 0.001). Based on receiver operating curve analysis, we derived a cut-off value of [Na+] − [Cl−] below 33.5 mEq/L. Using this cut off value, the sensitivity and specificity of [Na+] − [Cl−] for metabolic acidosis were 75.2% and 75.0%, respectively. To explore whether metabolic acidosis is associated with hyperkalemia after initiating ACE-I or ARB, we examined 1143 patients with CKD. Among this cohort, 403 (35.3%) patients had [Na+] − [Cl−] < 33.5 mEq/L at baseline, and the incidence of hyperkalemia was significantly higher in univariate analysis (9.2% versus 4.2%, p = 0.03). However, in multivariate analysis, [Na+] − [Cl−] < 33.5 mEq/L was not associated with hyperkalemia (odds ratio 1.13; 95% confidence interval 0.65–1.95). Conclusions Hyperchloremic metabolic acidosis was not associated with hyperkalemia after initiation of ACE-I or ARB in patients with CKD.