Low Serum Bicarbonate and CKD Progression in Children

Abstract

Background and objectives: Studies of adults have demonstrated an association between metabolic acidosis, as measured by low serum bicarbonate levels, and CKD progression. We evaluated this relationship in children using data from the Chronic Kidney Disease in Children study.

Design, setting, participants, & measurements: The relationship between serum bicarbonate and a composite end point, defined as 50% decline in eGFR or KRT, was described using parametric and semiparametric survival methods. Analyses were stratified by underlying nonglomerular and glomerular diagnoses, and adjusted for demographic characteristics, eGFR, proteinuria, anemia, phosphate, hypertension, and alkali therapy.

Results: Six hundred and three participants with nonglomerular disease contributed 2673 person-years of follow-up, and 255 with a glomerular diagnosis contributed 808 person-years of follow-up. At baseline, 39% (237 of 603) of participants with nonglomerular disease had a bicarbonate level of ≤22 meq/L and 36% (85 of 237) of those participants reported alkali therapy treatment. In participants with glomerular disease, 31% (79 of 255) had a bicarbonate of ≤22 meq/L, 18% (14 of 79) of those participants reported alkali therapy treatment. In adjusted longitudinal analyses, compared with participants with a bicarbonate level >22 meq/L, hazard ratios associated with a bicarbonate level of <18 meq/L and 19-22 meq/L were 1.28 [95% confidence interval (95% CI), 0.84 to 1.94] and 0.91 (95% CI, 0.65 to 1.26), respectively, in children with nonglomerular disease. In children with glomerular disease, adjusted hazard ratios associated with bicarbonate level ≤18 meq/L and bicarbonate 19-22 meq/L were 2.16 (95% CI, 1.05 to 4.44) and 1.74 (95% CI, 1.07 to 2.85), respectively. Resolution of low bicarbonate was associated with a lower risk of CKD progression compared with persistently low bicarbonate (≤22 meq/L).

Conclusions: In children with glomerular disease, low bicarbonate was linked to a higher risk of CKD progression. Resolution of low bicarbonate was associated with a lower risk of CKD progression. Fewer than one half of all children with low bicarbonate reported treatment with alkali therapy. Long-term studies of alkali therapy's effect in patients with pediatric CKD are needed.

Keywords: acidosis; alkalis; anemia; bicarbonates; chronic; chronic kidney disease; chronic metabolic acidosis; demography; glomerular filtration rate; hypertension; longitudinal studies; pediatrics; phosphates; proteinuria; renal insufficiency; renal progression; renal replacement therapy.

Copyright © 2020 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

Survival time to 50% decline in eGFR or KRT (transplant or dialysis) by “ever acidosis” following the first bicarbonate measurement among 603 participants with non-glomerular disease (left). Event-free time by acidosis persistence following the first visit after participants become acidotic among 338 participants with non-glomerular disease who were ever acidotic (right). Parametric Weibull or Lognormal distributions for each group with location (β) and scale (σ) and denoted as WE(β, σ) or LN(β, σ), respectively, are shown by dashed lines. Percentiles provided due to differences in the proportion of participants who reached the composite event. The relative percentile measure of association summarizes the difference in time (years) for the pth percentile of the exposed group (e.g., those with acidosis) compared to the unexposed group (e.g., those without acidosis).

Figure 2.

Survival time to 50% decline in eGFR or KRT (transplant or dialysis) by “ever acidosis” following the first bicarbonate measurement among 255 participants with glomerular disease (left). Event-free time by acidosis persistence following the first visit after participants become acidotic among 105 participants with glomerular disease who were ever acidotic (right). Parametric Lognormal distributions for each group with location (β) and scale (σ) and denoted as LN(β, σ) are represented by dashed lines. Percentiles provided due to differences in the proportion of participants who reached the composite event. The relative percentile measure of association summarizes the difference in time (years) for the pth percentile of the exposed group (e.g., those with acidosis) compared to the unexposed group (e.g., those without acidosis).