Yokoyama Jennifer S, Matsuda-Abedini Mina, Denburg Michelle R, Kumar Juhi, Warady Bradley A, Furth Susan L, Hooper Stephen R, Portale Anthony A, Perwad Farzana
Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA.
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA.
Kidney Med. 2020 May 26;2(4):398-406. doi: 10.1016/j.xkme.2020.03.005. eCollection 2020 Jul-Aug.
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.
Observational study.
702 children enrolled in the Chronic Kidney Disease in Children (CKiD) Study.
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]D).
Neurocognitive tests of intelligence, academic achievement, and executive functions.
Linear regression models to analyze the cross-sectional associations between logFGF-23, 25(OH)D, 1,25(OH)D, PTH, calcium, and phosphorus scores and the cognitive test scores of interest after adjustment for demographics, blood pressure, proteinuria, and kidney function.
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. In fully adjusted analyses, 25(OH)D, 1,25(OH)D, PTH, calcium, and phosphorus scores did not associate with cognitive test scores. In fully adjusted analyses, logFGF-23 was associated with abnormal test scores for attention regulation ( < 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 ( < 0.05) for Errors of Omission (β = 0.4 [0.1, 0.7]) and Hit Reaction Time (β = 0.4 [0.1, 0.7]).
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.
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.
儿童慢性肾脏病（CKD）与认知功能障碍相关，这会影响学业成绩和生活质量。儿童CKD-矿物质与骨代谢紊乱和认知功能之间的关系尚不清楚。
观察性研究。
702名参与儿童慢性肾脏病（CKiD）研究的儿童。
血浆成纤维细胞生长因子23（FGF-23）、甲状旁腺激素（PTH）、钙、磷、25羟维生素D（25[OH]D）和1,25二羟维生素D（1,25[OH]D）。
智力、学业成绩和执行功能的神经认知测试。
采用线性回归模型分析logFGF-23、25(OH)D、1,25(OH)D、PTH、钙和磷得分与经人口统计学、血压、蛋白尿和肾功能调整后的相关认知测试得分之间的横断面关联。
在基线时，中位年龄为12岁（95%CI，8.3，15.2），估计肾小球滤过率为54（40.5，67.8）mL/min/1.73m²。在完全调整分析中，25(OH)D、1,25(OH)D、PTH、钙和磷得分与认知测试得分无关。在完全调整分析中，logFGF-23与注意力调节测试异常得分相关（P<0.05）；具体而言，康纳斯连续操作测验II的遗漏错误（β=2.3[1.0，3.6]）、变异性（β=1.4[0.4，2.4]）和击中反应时间（β=1.3[0.2，2.4]）。FGF-23最高三分位数组的儿童在击中反应时间和遗漏错误方面的认知风险分别比最低三分位数组的儿童高7%和9%。在完全调整分析中，较高的FGF-23三分位数与遗漏错误（β=0.4[0.1，0.7]）和击中反应时间（β=0.4[0.1，0.7]）的认知风险增加相关（P<0.05）。
该研究未评估FGF-23过量随时间对认知功能的累积影响。由于样本量有限，未进行人群内分层分析。
在CKD儿童中，较高的血浆FGF-23水平与执行功能的靶向测试中较低的表现相关，特别是注意力调节，独立于肾小球滤过率。
