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

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, nonglomerular or glomerular. Results: The study population included 1082 children with CKD: 808 with nonglomerular etiologies and 274 with glomerular etiologies. Baseline serum bicarbonate levels ≤22 mEq/L were associated with worse height z scores in all children. Longitudinally, serum bicarbonate levels ≤18 and 19-22 mEq/L were associated with worse height z scores in children with nonglomerular CKD causes, with adjusted mean values of -0.39 (95% CI, -0.58 to -0.2) and -0.17 (95% CI, -0.28 to -0.05), respectively. Children with nonglomerular 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 evaluate this relationship prospectively.