Circulating Levels of Soluble Klotho and FGF23 in X-Linked Hypophosphatemia: Circadian Variance, Effects of Treatment, and Relationship to Parathyroid Status
Circulating Levels of Soluble Klotho and FGF23 in X-Linked Hypophosphatemia: Circadian Variance, Effects of Treatment, and Relationship to Parathyroid Status
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DOI：
10.1210/jc.2010-0589
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发表时间：
2010-11-01
影响因子：
5.8
通讯作者：
Gundberg, Caren M.
中科院分区：
文献类型：
--
作者：
Carpenter, Thomas O.;Insogna, Karl L.;Gundberg, Caren M.
内容：循环成纤维细胞生长因子（FGF）-23在X连锁低磷酸盐血症（XLH）的个体中显著升高，klotho最近已被证明可以影响肾磷酸盐处理，但有关循环FGF 23和klotho in XLH.Objective：本研究的目的是表征循环FGF 23和klotho in XLH.Design：XLH的儿童和成人拒绝药物治疗14 d。获得空腹血清FGF 23、PTH、klotho、磷酸盐和1，25二羟维生素D。治疗的成年人也进行了抽样，并在选定的个体进行昼夜节律抽样。设置：该研究在一个学术医疗中心的医院研究单位进行。患者和其他参与者：参与者包括23名XLH患者和8名对照。干预措施：没有干预措施。主要结果测量：血清klotho和FGF 23进行了测量。结果：XLH组的FGF 23高于对照组，治疗组的FGF 23高于未接受药物治疗的XLH组。儿童的klotho水平高于成人，但XLH值与对照组相似。在XLH受试者中发现FGF 23和PTH之间存在很强的正相关性，而在对照组中这些变量之间没有关系。循环klotho，而不是FGF 23，具有昼夜模式。结论：血清klotho随着年龄的增长而下降，并表现出昼夜变化，但在XLH是正常的。血清FGF 23在儿童和成人中相似，在XLH中升高，随着治疗进一步升高，并且没有昼夜变化。XLH受试者中FGF 23和PTH之间的直接关系表明，在这种疾病中，FGF 23对PTH分泌的调节是异常的。（临床内分泌代谢杂志95：E352-E357，2010）
Context: Circulating fibroblast growth factor (FGF)-23 is variably elevated in individuals with X-linked hypophosphatemia (XLH), and klotho has recently been shown to effect renal phosphate handling, yet limited data are available on circulating FGF23 and klotho in XLH.Objective: The objective of the study was to characterize circulating FGF23 and klotho in XLH.Design: Children and adults with XLH withheld medication for 14 d. Fasting serum FGF23, PTH, klotho, phosphate, and 1,25 dihydroxyvitamin D were obtained. Treated adults were also sampled, and circadian sampling was performed in selected individuals.Setting: The study was conducted at a hospital research unit at an academic medical center.Patients and Other Participants: Participants included 23 individuals with XLH and eight controls.Interventions: There were no interventions.Main Outcome Measures: Serum klotho and FGF23 were measured.Results: FGF23 was greater in XLH than in controls and greater in treated XLH subjects compared with XLH subjects not receiving medical therapy. Children had higher klotho levels than adults, but values in XLH were similar to controls. A strong positive correlation between FGF23 and PTH was found in XLH subjects, whereas there was no relationship between these variables in controls. Circulating klotho, but not FGF23, has a diurnal pattern.Conclusions: Serum klotho declines with age and demonstrates circadian variation but is normal in XLH. Serum FGF23 is similar in children and adults, is elevated in XLH, further increases with therapy, and demonstrates no diurnal variation. The direct relationship between FGF23 and PTH in subjects with XLH suggests that FGF23 regulation of PTH secretion is aberrant in this disorder. (J Clin Endocrinol Metab 95: E352-E357, 2010)