Longitudinal Associations between Low Serum Bicarbonate and Linear Growth in Children with CKD

Abstract

Background: Poor linear growth is a consequence of chronic kidney disease (CKD) that has been linked to adverse outcomes. Metabolic acidosis (MA) has been identified as a risk factor for growth failure. We investigated the longitudinal relationship between MA and linear growth in children with CKD and examined whether treatment of MA modified linear growth. Methods: To describe longitudinal associations between MA and linear growth, we used serum bicarbonate levels, height measurements and standard deviation (z-scores) of children enrolled in the prospective cohort study, Chronic Kidney Disease in Children. Analyses were adjusted for covariates recognized as correlating with poor growth including demographic characteristics, glomerular filtration rate (GFR), proteinuria, calcium, phosphate, parathyroid hormone, and CKD duration. CKD diagnoses were analyzed by disease categories, non-glomerular or glomerular. Results: The study population included 1082 children with CKD: 808 with non-glomerular etiologies and 274 with glomerular etiologies. Baseline serum bicarbonate levels {less than/equal to}22mEq/L were associated with worse height z-scores in all children. Longitudinally, serum bicarbonate levels {less than/equal to}18mEq/L and 19-22mEq/L were associated with worse height z-scores in children with non-glomerular CKD causes, with adjusted mean values of -0.39, (95%CI: -0.58, -0.20) and -0.17, (95%CI: -0.28, -0.05), respectively. Children with non-glomerular disease and more severe GFR impairment had a higher risk for worse height z-score. A significant association was not found in children with glomerular diseases. We also investigated the potential effect of treatment of MA on height in children with a history of alkali therapy use finding that only persistent users had a significant positive association between their height z-score and higher serum bicarbonate levels. Conclusions: We observed a longitudinal association between MA and lower height z-score. Additionally, persistent alkali therapy use was associated with better height z-scores. Future clinical trials of alkali therapy need to prospectively evaluate this relationship.

Impact of Metabolic Acidosis and Alkali Therapy on Linear Growth in Children with Chronic Kidney Disease: What Is the Current Evidence?

“…Despite these limitations, this study by Brown et al . (26) presents clinically relevant evidence of the deleterious effect of metabolic acidosis on growth in children with CKD. The study also underscores the importance of alkali therapy on improved growth in this cohort.…”

“…The study by Brown et al . (26) aims to fill this knowledge gap and reports novel findings that treatment of metabolic acidosis with alkali therapy improves growth in children with CKD.…”

“…In this issue of Kidney360 , Brown et al . (26) seek to characterize better the effect of metabolic acidosis, and treatment with alkali therapy, on linear growth in a large cohort of children with CKD in a longitudinal observational cohort study. The authors analyzed data from the Chronic Kidney Disease in Children (CKiD) study—a prospective, multicenter cohort of children with mild-moderate kidney impairment (eGFR 30–90 ml/min per 1.73 m 2 ) (27).…”