Association Between Chronic Kidney Disease-Mineral Bone Disease (CKD-MBD) and Cognition in Children: Chronic Kidney Disease in Children (CKiD) Study

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](2)D). Outcomes: Neurocognitive tests of intelligence, academic achievement, and executive functions. Analytical Approach: Linear regression models to analyze the cross-sectional associations between log(2)FGF-23, 25(OH)D, 1,25(OH)(2)D, 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 m(2). In fully adjusted analyses, 25(OH)D, 1,25(OH)(2)D, PTH, calcium, and phosphorus z scores did not associate with cognitive test scores. In fully adjusted analyses, log(2)FGF-23 was associated with abnormal test scores for attention regulation (P < 0.05); specifically, Conners' Continuous Performance Test II Errors of Omission (beta = 2.3 [1.0, 3.6]), Variability (beta = 1.4 [0.4, -2.4]), and Hit Reaction Time (beta = 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 (beta = 0.4 [0.1, 0.7]) and Hit Reaction Time (beta = 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.