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Original ArticlesChronic Kidney Disease
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Low Serum Bicarbonate and CKD Progression in Children

Denver D. Brown, Jennifer Roem, Derek K. Ng, Kimberly J. Reidy, Juhi Kumar, Matthew K. Abramowitz, Robert H. Mak, Susan L. Furth, George J. Schwartz, Bradley A. Warady, Frederick J. Kaskel and Michal L. Melamed
CJASN June 2020, 15 (6) 755-765; DOI: https://doi.org/10.2215/CJN.07060619
Denver D. Brown
1Division of Pediatric Nephrology, Children’s National Hospital, Washington, DC
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Jennifer Roem
2Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
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Derek K. Ng
2Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
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Kimberly J. Reidy
3Division of Pediatric Nephrology, The Children’s Hospital at Montefiore, Bronx, New York
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Juhi Kumar
4Division of Pediatric Nephrology, Weill Cornell Medicine, New York, New York
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Matthew K. Abramowitz
5Department of Medicine, Albert Einstein College of Medicine, Bronx, New York
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Robert H. Mak
6Division of Pediatric Nephrology, Rady Children’s Hospital San Diego, University of California San Diego, San Diego, California
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Susan L. Furth
7Division of Pediatric Nephrology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
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George J. Schwartz
8Division of Pediatric Nephrology, University of Rochester, Rochester, New York
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Bradley A. Warady
9Division of Pediatric Nephrology, Children’s Mercy Hospital, Kansas City, Missouri
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Frederick J. Kaskel
3Division of Pediatric Nephrology, The Children’s Hospital at Montefiore, Bronx, New York
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Michal L. Melamed
5Department of Medicine, Albert Einstein College of Medicine, Bronx, New York
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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.

  • chronic kidney disease
  • chronic metabolic acidosis
  • pediatrics
  • renal progression
  • bicarbonates
  • phosphates
  • alkalis
  • renal insufficiency
  • chronic
  • longitudinal studies
  • proteinuria
  • glomerular filtration rate
  • renal replacement therapy
  • anemia
  • acidosis
  • hypertension
  • demography
  • Received June 14, 2019.
  • Accepted April 9, 2020.
  • Copyright © 2020 by the American Society of Nephrology
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Clinical Journal of the American Society of Nephrology: 15 (6)
Clinical Journal of the American Society of Nephrology
Vol. 15, Issue 6
June 08, 2020
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Low Serum Bicarbonate and CKD Progression in Children
Denver D. Brown, Jennifer Roem, Derek K. Ng, Kimberly J. Reidy, Juhi Kumar, Matthew K. Abramowitz, Robert H. Mak, Susan L. Furth, George J. Schwartz, Bradley A. Warady, Frederick J. Kaskel, Michal L. Melamed
CJASN Jun 2020, 15 (6) 755-765; DOI: 10.2215/CJN.07060619

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Low Serum Bicarbonate and CKD Progression in Children
Denver D. Brown, Jennifer Roem, Derek K. Ng, Kimberly J. Reidy, Juhi Kumar, Matthew K. Abramowitz, Robert H. Mak, Susan L. Furth, George J. Schwartz, Bradley A. Warady, Frederick J. Kaskel, Michal L. Melamed
CJASN Jun 2020, 15 (6) 755-765; DOI: 10.2215/CJN.07060619
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Keywords

  • chronic kidney disease
  • chronic metabolic acidosis
  • pediatrics
  • renal progression
  • bicarbonates
  • phosphates
  • alkalis
  • renal insufficiency
  • Chronic
  • longitudinal studies
  • proteinuria
  • glomerular filtration rate
  • renal replacement therapy
  • anemia
  • acidosis
  • hypertension
  • Demography

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