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A longitudinal analysis of the effect of anemia on executive functions in children with mild to moderate chronic kidney disease

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Abstract

Background

Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction. The aim of this study was to investigate associations between executive functions (EF), anemia, and iron deficiency.

Methods

A total of 688 children > 6 years of age enrolled in the Chronic Kidney Disease in Children (CKiD) study who underwent evaluation for EF were included. Hemoglobin (Hgb) was characterized as low (1st–5th percentile) or very low (< 1st percentile) compared to normative values for age, sex, and race irrespective of erythropoiesis-stimulating agent (ESA) usage. Longitudinal analysis was conducted using consecutive visit pairs, with anemia status defined as new onset, resolved, or persistent. Linear mixed models with random intercept were used and adjusted for key covariates.

Results

Anemia was present in 41% of children, and median Hgb was 11.8 gm/dl. New onset anemia was associated with lower digit span total score (− 0.75, 95% CI − 1.36, − 0.15, p = 0.01). Persistent anemia was associated with lower scores on color-word inhibition/switching (β =  − 0.98; 95% CI − 1.78, − 0.18, p = 0.02). Errors of omission were significantly higher (worse) in those with persistent anemia (β = 2.67, 95% CI 0.18, 5.17, p = 0.04). Very low Hgb levels were significantly associated with lower color-word inhibition/switching scores (β =  − 1.33, 95% CI − 2.16, − 0.51; p = 0.002). Anemia and low GFR were associated with lower category fluency scores compared to non-anemic subjects with higher GFR (β =  − 1.09, 95% CI − 2.09, − 0.10, p = 0.03).

Conclusions

The presence of anemia, in addition to its severity and duration in children with CKD, is associated with poorer scores on select measures of EF.

Graphical abstract

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Acknowledgements

Data in this manuscript were collected by the CKiD prospective cohort study with clinical coordinating centers (principal investigators) at Children’s Mercy Hospital and the University of Missouri–Kansas City (Dr. Bradley Warady) and the Children’s Hospital of Philadelphia (Dr. Susan Furth), the Central Biochemistry Laboratory (Dr. George Schwartz) at the University of Rochester Medical Center, and the data coordinating center (Drs. Alvaro Muñoz and Derek Ng) at the Johns Hopkins Bloomberg School of Public Health. The CKiD website is located at https://statepi.jhsph.edu/ckid, and a list of CKiD collaborators can be found at https://statepi.jhsph.edu/ckid/site-investigators/. Please refer to the supplemental document which contains the list of the site principal investigators.

Funding

The CKiD Study is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01-DK-66143, U01-DK-66174, U24-DK-082194, U24-DK-66116). The CKiD website is located at https://statepi.jhsph.edu/ckid and a list of CKiD collaborators can be found at https://statepi.jhsph.edu/ckid/site-investigators/.

Author information

Authors and Affiliations

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

    Nisha S. Singh & Bradley A. Warady

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

    Rebecca J. Johnson

  3. Division of Developmental and Behavioral Health, Children’s Mercy Kansas City, Kansas City, MO, USA

    Matthew B. Matheson

  4. Division of Pediatric Nephrology and Hypertension, Department of Pediatrics, Rutgers/Robert Wood Johnson Medical School, New Brunswick, NJ, USA

    Joann Carlson

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

    Stephen R. Hooper

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  1. Nisha S. Singh
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Correspondence to Nisha S. Singh.

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Singh, N.S., Johnson, R.J., Matheson, M.B. et al. A longitudinal analysis of the effect of anemia on executive functions in children with mild to moderate chronic kidney disease. Pediatr Nephrol 38, 829–837 (2023). https://doi.org/10.1007/s00467-022-05682-3

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  • DOI: https://doi.org/10.1007/s00467-022-05682-3

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