DOI: 10.1016/j.xkme.2020.03.005; PMCID: PMC7406846
Rationale & objective: Chronic kidney disease (CKD) in children is associated with cognitive dysfunction that affects school performance and quality of life. The relationship between CKD-mineral and bone disorder and cognitive function in children is unknown.
Study design: Observational study.
Participants: 702 children enrolled in the Chronic Kidney Disease in Children (CKiD) Study.
Predictors: Plasma fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), calcium, phosphorus, 25 hydroxyvitamin D (25[OH]D), and 1,25 dihydroxyvitamin D (1,25[OH]2D).
Outcomes: Neurocognitive tests of intelligence, academic achievement, and executive functions.
Analytical approach: Linear regression models to analyze the cross-sectional associations between log2FGF-23, 25(OH)D, 1,25(OH)2D, PTH, calcium, and phosphorus z scores and the cognitive test scores of interest after adjustment for demographics, blood pressure, proteinuria, and kidney function.
Results: At baseline, median age was 12 (95% CI, 8.3, 15.2) years and estimated glomerular filtration rate was 54 (40.5, 67.8) mL/min/1.73 m2. In fully adjusted analyses, 25(OH)D, 1,25(OH)2D, PTH, calcium, and phosphorus z scores did not associate with cognitive test scores. In fully adjusted analyses, log2FGF-23 was associated with abnormal test scores for attention regulation (P < 0.05); specifically, Conners' Continuous Performance Test II Errors of Omission (β = 2.3 [1.0, 3.6]), Variability (β=1.4 [0.4, -2.4]), and Hit Reaction Time (β = 1.3 [0.2, 2.4]). Children in the highest FGF-23 tertile group had 7% and 9% greater cognitive risk for Hit Reaction Time and Errors of Omission compared with those in the lowest tertile, respectively. In fully adjusted analyses, higher FGF-23 tertile was associated with increased cognitive risk (P < 0.05) for Errors of Omission (β = 0.4 [0.1, 0.7]) and Hit Reaction Time (β = 0.4 [0.1, 0.7]).
Limitations: The study does not assess the cumulative effects of FGF-23 excess on cognitive function over time. Within-population stratified analyses were not performed due to limited sample size.
Conclusions: In children with CKD, higher plasma FGF-23 level is associated with lower performance in targeted tests of executive function, specifically attention regulation, independent of glomerular filtration rate.
FGF-23; chronic kidney disease; cognition; pediatric
Yokoyama, J. S., Matsuda-Abedini, M., Denburg, M. R., Kumar, J., Warady, B. A., Furth, S. L., Hooper, S. R., Portale, A. A., Perwad, F. Association Between Chronic Kidney Disease-Mineral Bone Disease (CKD-MBD) and Cognition in Children: Chronic Kidney Disease in Children (CKiD) Study. Kidney Med 2, 398-406 (2020).