Skip to main content
SpringerLink
Log in

Bicarbonate, blood pressure, and executive function in pediatric CKD—is there a link?

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

In adult chronic kidney disease (CKD), metabolic acidosis is associated with diminished cognition, notably executive function (EF). Data from the Chronic Kidney Disease in Children (CKiD) study demonstrate a risk for impairment of EF, a finding associated with heightened blood pressure variability (BPV). We sought to determine whether low serum bicarbonate is also associated with performance on tests of EF in pediatric CKD and to investigate potential interaction with BPV.

Methods

CKiD participants with serum bicarbonate, blood pressure, and selected cognitive measurements available were evaluated. An EF summary score was derived from scores on the Delis-Kaplan Executive Function System, Conners’ Continuous Performance Test, and Digit Span Backwards subtest from the Wechsler Intelligence Scale for Children-IV-Integrated. Parents completed the Behavioral Rating Inventory of Executive Function (BRIEF) to yield a Global Executive Composite (GEC) score. Linear mixed models with bicarbonate and hypertension as predictors and linear regression with bicarbonate and BPV were used to predict EF level.

Results

Data were available for 865 children. Twenty-two percent had low bicarbonate (CO2 ≤ 20 mmol/L) at baseline. On multivariate analysis, there was no relationship between bicarbonate, hypertension, and EF. There was no significant CO2×hypertension interaction found. A significant interaction (p = 0.01) between high CO2 (≥ 26 mmol/L) and BPV was detected in the model with GEC as the EF outcome, indicating that while higher BPV was associated with worse EF in the low and normal CO2 groups, higher BPV was associated with better EF in the high CO2 group.

Conclusions

Our analyses revealed an interaction between one measure of BPV and low bicarbonate on neurocognition in pediatric CKD, suggesting a potential role for control of both bicarbonate and blood pressure in preserving cognition in early CKD. Further research is needed to confirm and further define this association.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Kovesdy CP, Anderson JE, Kalantar-Zadeh K (2009) Association of serum bicarbonate levels with mortality in patients with non-dialysis-dependent CKD. Nephrol Dial Transplant 24(4):1232–1237

    Article  CAS  Google Scholar 

  2. Wu DY et al (2006) Association between serum bicarbonate and death in hemodialysis patients: is it better to be acidotic or alkalotic? Clin J Am Soc Nephrol 1(1):70–78

    Article  CAS  Google Scholar 

  3. Li F et al (2011) Acidosis leads to brain dysfunctions through impairing cortical GABAergic neurons. Biochem Biophys Res Commun 410(4):775–779

    Article  CAS  Google Scholar 

  4. Song R et al (2011) Acidosis and alkalosis impair brain functions through weakening spike encoding at cortical GABAergic neurons. J Neurol Sci 304(1–2):122–126

    Article  CAS  Google Scholar 

  5. Dobre M et al (2018) Serum bicarbonate concentration and cognitive function in hypertensive adults. Clin J Am Soc Nephrol 13(4):596–603

    Article  CAS  Google Scholar 

  6. Hooper SR et al (2011) Neurocognitive functioning of children and adolescents with mild-to-moderate chronic kidney disease. Clin J Am Soc Nephrol 6(8):1824–1830

    Article  Google Scholar 

  7. Mendley SR et al (2015) Duration of chronic kidney disease reduces attention and executive function in pediatric patients. Kidney Int 87(4):800–806

    Article  Google Scholar 

  8. Lande MB et al (2016) Association of blood pressure variability and neurocognition in children with chronic kidney disease. Pediatr Nephrol 31(11):2137–2144

    Article  Google Scholar 

  9. Furth SL et al (2006) Design and methods of the Chronic Kidney Disease in Children (CKiD) prospective cohort study. Clin J Am Soc Nephrol 1(5):1006–1015

    Article  Google Scholar 

  10. Schwartz GJ et al (2012) Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney Int 82(4):445–453

    Article  CAS  Google Scholar 

  11. Flynn JT et al (2008) Blood pressure in children with chronic kidney disease: a report from the Chronic Kidney Disease in Children study. Hypertension 52(4):631–637

    Article  CAS  Google Scholar 

  12. Hastie CE et al (2013) Long-term and ultra long-term blood pressure variability during follow-up and mortality in 14,522 patients with hypertension. Hypertension 62(4):698–705

    Article  CAS  Google Scholar 

  13. Yano Y et al (2014) Long-term blood pressure variability throughout young adulthood and cognitive function in midlife: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Hypertension 64(5):983–988

    Article  CAS  Google Scholar 

  14. Boedtkjer E et al (2016) Extracellular HCO3- is sensed by mouse cerebral arteries: regulation of tone by receptor protein tyrosine phosphatase gamma. J Cereb Blood Flow Metab 36(5):965–980

    Article  CAS  Google Scholar 

  15. Setiadi A et al (2018) The role of the blood-brain barrier in hypertension. Exp Physiol 103(3):337–342

    Article  CAS  Google Scholar 

  16. de Leeuw FE et al (2002) Hypertension and cerebral white matter lesions in a prospective cohort study. Brain 125(Pt 4):765–772

    Article  Google Scholar 

  17. Shimoji K et al (2014) Diffusional kurtosis imaging analysis in patients with hypertension. Jpn J Radiol 32(2):98–104

    Article  Google Scholar 

  18. Li X et al (2016) Disrupted white matter structure underlies cognitive deficit in hypertensive patients. Eur Radiol 26(9):2899–2907

    Article  Google Scholar 

  19. Rasbury WC, Fennell RS 3rd, Morris MK (1983) Cognitive functioning of children with end-stage renal disease before and after successful transplantation. J Pediatr 102(4):589–592

    Article  CAS  Google Scholar 

  20. Brouhard BH et al (2000) Cognitive functioning in children on dialysis and post-transplantation. Pediatr Transplant 4(4):261–267

    Article  CAS  Google Scholar 

  21. Duquette PJ et al (2007) Brief report: intellectual and academic functioning in pediatric chronic kidney disease. J Pediatr Psychol 32(8):1011–1017

    Article  Google Scholar 

Download references

Acknowledgments

Data in this manuscript were collected by the CKiD prospective cohort study (CKiD) with clinical coordinating centers (Principal Investigators) at Children’s Mercy Hospital and the University of Missouri—Kansas City (Bradley Warady, MD) and Children’s Hospital of Philadelphia (Susan Furth, MD, PhD), Central Biochemistry Laboratory (George Schwartz, MD) at the University of Rochester Medical Center, and data coordinating center (Alvaro Muñoz, PhD) at the Johns Hopkins Bloomberg School of Public Health. The CKID website is located at http://www.statepi.jhsph.edu/ckid.

Funding

CKiD is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01-DK-66143, U01-DK-66174, U01DK-082194, U01-DK-66116). Dr. Harshman is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK110443).

Author information

Authors and Affiliations

  1. Division of Pediatric Nephrology, University of Iowa Stead Family Department of Pediatrics, 4037 Boyd Tower, 200 Hawkins Drive, Iowa City, IA, 52242, USA

    Lyndsay A. Harshman

  2. Division of Nephrology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Amy J. Kogon & Susan L. Furth

  3. Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Amy J. Kogon & Susan L. Furth

  4. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Matthew B. Matheson

  5. Division of Developmental and Behavioral Health, Children’s Mercy Kansas City, University of Missouri Kansas City School of Medicine, Kansas City, MO, USA

    Rebecca J. Johnson

  6. Departments of Neurology, Pediatrics and Epidemiology and Population Health, Montefiore Medical Center, Albert Einstein College of Medicine, New York City, NY, USA

    Shlomo Shinnar

  7. Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Arlene C. Gerson

  8. Division of Pediatric Nephrology, Children’s Mercy Kansas City, Kansas City, MO, USA

    Bradley A. Warady

  9. Department of Allied Health Sciences, School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA

    Stephen R. Hooper

  10. University of Rochester Medical Center, Rochester, NY, USA

    Marc B. Lande

Authors
  1. Lyndsay A. Harshman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amy J. Kogon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Matthew B. Matheson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rebecca J. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shlomo Shinnar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Arlene C. Gerson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bradley A. Warady
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Susan L. Furth
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Stephen R. Hooper
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Marc B. Lande
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lyndsay A. Harshman.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harshman, L.A., Kogon, A.J., Matheson, M.B. et al. Bicarbonate, blood pressure, and executive function in pediatric CKD—is there a link?. Pediatr Nephrol 35, 1323–1330 (2020). https://doi.org/10.1007/s00467-020-04507-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-020-04507-5

Keywords

Search

Navigation