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Kidney Week

Abstract: SA-PO435

Fibroblast Growth Factor 23 Is Associated with Impaired Cognition in Children with CKD

Session Information

  • Pediatric Nephrology - II
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1600 Pediatric Nephrology

Authors

  • Yokoyama, Jennifer S., University of California, San Francisco, San Francisco, California, United States
  • Matsuda-Abedini, Mina, The Hospital for Sick Children, Toronto, Toronto, Ontario, Canada
  • Warady, Bradley A., Children's Mercy Kansas City , Kansas City, Missouri, United States
  • Furth, Susan L., The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Hooper, Stephen R., University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States
  • Portale, Anthony A., University of California San Francisco, San Francisco, California, United States
  • Perwad, Farzana, University of California San Francisco, San Francisco, California, United States
Background

Plasma FGF23 concentrations increase early in the course of chronic kidney disease (CKD) in children and are a strong predictor of disease progression and left ventricular hypertrophy. High plasma FGF23 has been linked to cognitive dysfunction and cerebrovascular disease in adults with CKD. Whether FGF23 associates with impaired cognition in children is unknown.

Methods

In 538 children with CKD stages 2-4 enrolled in the Chronic Kidney Disease in Children (CKiD) study, we measured plasma C-terminal FGF23 and phosphorus and performed cognitive function tests of intelligence, academic achievement, and targeted executive functions. We used multivariate linear regression to analyze cross-sectional associations of baseline FGF23 and phosphorus concentrations with standardized cognitive test scores and cognitive risk (defined as a score ≥1 standard deviation (SD) below mean performance for age in healthy children), adjusting for age, sex, race, estimated GFR, proteinuria, blood pressure, and anemia.

Results

At baseline, median age was 12 [95% CI: 8.3, 15.2] years, eGFR was 54 [40.5, 67.8] ml/min/1.73 m2, plasma FGF23 and phosphorus were 168 [78, 175] RU/ml and 4.2 [4, 4.9] mg/dl, respectively. In univariate analyses, higher tertiles of FGF23 were associated significantly with impaired test scores for errors of omission, a measure of attention regulation (p=0.002, 2-tailed Kruskal-Wallis rank test), and academic achievement (p=0.06). In fully adjusted analyses, we observed that each 50% increase in plasma FGF23 was associated with a 1 SD worsening of omission scores (β=2.07 [0.7-3.4], p=0.003). The percentage of children at risk for one or more cognitive deficits ranged from 18 to 32%. Furthermore, the cognitive risk for errors of omission was 14% higher in children in the highest compared to the lowest FGF23 tertile (p=0.01, 2-tailed chi-squared test). Plasma phosphorus, normalized for age, did not associate with cognitive test scores or cognitive risk.

Conclusion

In children with pre-dialysis CKD, higher baseline plasma FGF23 is associated with lower performance in targeted tests of executive function, specifically attention regulation, independent of GFR. These data suggest that high plasma FGF23 contributes to a greater risk for disorders of attention regulation as GFR declines.