Metabolic Acidosis and Cardiovascular Disease Risk in Children with CKD.

Abstract

Background: The link between metabolic acidosis (MA) and cardiovascular disease (CVD) outcomes has been studied in adults but not in children with CKD where MA is a common and early finding. Using longitudinal blood pressure (BP) and cardiac measurement data, we evaluated whether low serum bicarbonate (a surrogate for MA) is associated with adverse CVD risk.

Methods: This study used data from children 1 year of age and older with estimated glomerular filtration rates (eGFR) between 30-90 ml/min per 1.73m2 at enrollment into the Chronic Kidney Disease in Children (CKiD) study. Linear regression models were used to characterize the association between serum bicarbonate, resting and ambulatory BP measurements (ABPM), and indexed left ventricular mass measurements (LVMI). To compare BPs across children of different age/sex/height, BPs were indexed by dividing their average BP by the appropriate hypertensive threshold. Analyses allowed serum bicarbonate to be time varying and were adjusted for relevant demographic and clinical covariates.

Results: The study population consisted of 936 children who contributed data from 2581 paired visits. All had resting BP, 674 had ABPM measurements, and 736 had LVMI measurements. In fully adjusted models, there was an association between lower serum bicarbonate and higher resting BP. Lower serum bicarbonate level was also associated with lower ABPM wake and sleep systolic indices, and a small but significant increase in LVMI, 0.02 (95% CI: 0.004, 0.05).

Conclusions: We observed an association between MA and higher resting BP, lower ABPM, and higher LVMI. Future studies should address MA and CVD risk across the spectrum of CKD severity, incorporate additional assessments of CVD risk such as pulse wave velocity and carotid intima media thickness. Future studies should also test whether alkali therapy treatment, and the resolution of MA, mitigates these observed associations.