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, 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.

Keywords: child; chronic kidney disease; growth; serum bicarbonate.

Conflict of interest statement

M. Carroll reports ownership interest in Verily Life Sciences and research funding from Verily Life Sciences. A. Dauber reports ownership interest in Ascendis, Biomarin, and Novo Nordisk and research funding from Biomarin. L.A. Greenbaum reports consultancy for Abbvie, Advicenne, Alexion, Arrowhead Pharmaceuticals, Aurinia, CorMedix, NephroDI Therapeutics, Natera, Novartis, Roche, and Otsuka; research funding from Abbvie, Advicenne, Alexion, Apellis, Aurinia, Horizon Pharmaceuticals, Reata Pharmaceuticals, and Vertex; honoraria from Alexion; an advisory or leadership role with Alexion; and other interests or relationships (DSMB payments) with Akebia, Alnylam, Relypsa, Travere, and UCSD. F.J. Kaskel reports research funding from NIDDK and an advisory or leadership role for Frost Valley YMCA and Nephcure, Inc. M.L. Melamed reports an advisory or leadership role for the American Board of Internal Medicine Nephrology Exam Committee and has other interests in or relationships with the American Society of Nephrology and the New York Society of Nephrology. D.K. Ng reports consultancy for Ashvattha Therapeutics. B.A. Warady reports consultancy for Amgen, Bayer, Lightline Medical, Reata, Relypsa, and UpToDate; research funding from Baxter Healthcare; honoraria from Amgen, Bayer, Reata, Relypsa, and UpToDate; and an advisory or leadership role with the Midwest Transplant Network Governing Board, the National Kidney Foundation, North American Pediatric Renal Trials and Collaborative Studies, and the NTDS Board of Directors. All remaining authors have nothing to disclose.

Copyright © 2022 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

Distribution of height z score by previous visit bicarbonate levels among person-visits contributed by participants. (A) Participants with a diagnosis of nonglomerular CKD. (B) Participants with a diagnosis of glomerular CKD.