Metabolic Acidosis and Cardiovascular Disease Risk in Children with CKD

Key Points Metabolic acidosis may be associated with adverse cardiovascular disease risk. Prospective studies of the benefit of alkali therapy on cardiovascular disease risk are needed. 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 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 age 1 year and older with eGFRs between 30 and 90 ml/min per 1.73 m 2 at enrollment into the CKD in Children study. Linear regression models were used to characterize the association between serum bicarbonate, resting and ambulatory BP monitoring (ABPM) measurements, and indexed left ventricular mass measurements (left ventricular mass index [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% confidence interval. 0.004 to 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 and 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.