慢性肾脏病儿童中紊乱的成纤维细胞生长因子 23 和矿物质代谢。
Disordered FGF23 and mineral metabolism in children with CKD.
机构信息
Department of Pediatrics, University of California, San Francisco, California;, †Department of Medicine and, §Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, Florida;, ‡Department of Pediatrics, Harvard Medical School, Boston, Massachusetts;, ‖Department of Pediatrics, Weill Cornell Medical College, New York, New York;, ¶Department of Pediatrics, University of California, Los Angeles, California;, *Department of Pediatrics, University of Rochester School of Medicine, Rochester, New York;, ††Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, ‡‡Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
出版信息
Clin J Am Soc Nephrol. 2014 Feb;9(2):344-53. doi: 10.2215/CJN.05840513. Epub 2013 Dec 5.
BACKGROUND AND OBJECTIVES
In children with CKD, information is limited regarding the prevalence and determinants of fibroblast growth factor 23 excess and 1,25-dihyroxyvitamin D deficiency across the spectrum of predialysis CKD. This study characterized circulating concentrations of fibroblast growth factor 23 and 1,25-dihyroxyvitamin D, and investigated their interrelationships and associations with GFR and secondary hyperparathyroidism in children with CKD who were enrolled in the Chronic Kidney Disease in Children observational cohort study.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma fibroblast growth factor 23 concentrations and determinants of mineral metabolism were measured in 464 children ages 1-16 years with predialysis CKD. GFR was measured by plasma disappearance of iohexol in 70% of participants and estimated by the Chronic Kidney Disease in Children estimating equation using serum creatinine and cystatin C concentrations in the remainder of the participants. Participants were grouped according to CKD stage and by 10-ml/min categories of GFR.
RESULTS
Median GFR for the cohort was 45 ml/min per 1.73 m(2) (interquartile range=33-57; range=15-109). Plasma fibroblast growth factor 23 concentration was above the normal range in 67% of participants (with higher levels observed among participants with lower GFR) before higher levels of serum parathyroid hormone and phosphorus were observed. Plasma fibroblast growth factor 23 levels were 34% higher in participants with glomerular disease than in participants with nonglomerular disease, despite similar GFR. Serum phosphorus levels, adjusted for age, were significantly lower at GFR of 60-69 ml/min per 1.73 m(2) than higher GFR, but thereafter they became higher in parallel with fibroblast growth factor 23 as GFR declined. Serum 1,25-dihyroxyvitamin D concentrations were lower in those participants with low GFR values, high fibroblast growth factor 23 levels, 25-hydroxyvitamin D deficiency, and proteinuria. Secondary hyperparathyroidism was present in 55% of participants with GFR<50 ml/min per 1.73 m(2).
CONCLUSION
In children with predialysis CKD, high plasma fibroblast growth factor 23 is the earliest detectable abnormality in mineral metabolism, and levels are highest in glomerular diseases.
背景和目的
在患有慢性肾脏病（CKD）的儿童中，关于纤维母细胞生长因子 23（FGF23）过量和 1,25-二羟维生素 D 缺乏在整个 CKD 前期的流行率和决定因素的信息有限。本研究描述了在接受慢性肾脏病儿童观察队列研究的 CKD 前期儿童中循环 FGF23 和 1,25-二羟维生素 D 的浓度，并研究了它们与 GFR 和继发性甲状旁腺功能亢进之间的相互关系和关联。
设计、地点、参与者和测量：在 464 名年龄在 1-16 岁的 CKD 前期儿童中，测量了血浆 FGF23 浓度和矿物质代谢的决定因素。70%的参与者通过血浆 iohexol 消失率测量 GFR，其余参与者通过慢性肾脏病儿童估计方程，利用血清肌酐和胱抑素 C 浓度来估计 GFR。参与者根据 CKD 分期和 GFR 的 10ml/min 分类进行分组。
结果
队列的平均 GFR 为 45ml/min/1.73m2（四分位间距=33-57；范围=15-109）。在观察到更高水平的甲状旁腺激素和磷之前，67%的参与者（GFR 较低的参与者水平较高）的血浆 FGF23 浓度超出正常范围。尽管肾小球疾病患者的 GFR 相似，但与非肾小球疾病患者相比，肾小球疾病患者的血浆 FGF23 水平高出 34%。在 GFR 为 60-69ml/min/1.73m2 时，调整年龄后的血清磷水平显著低于较高的 GFR，但此后随着 GFR 下降，血清磷水平与 FGF23 平行升高。在 GFR 值较低、FGF23 水平较高、25-羟维生素 D 缺乏和蛋白尿的患者中，血清 1,25-二羟维生素 D 浓度较低。55%的 GFR<50ml/min/1.73m2 的参与者存在继发性甲状旁腺功能亢进。
结论
在 CKD 前期儿童中，高血浆 FGF23 是矿物质代谢中最早可检测到的异常，在肾小球疾病中水平最高。
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