Circulating Fibroblast Growth Factor 23 in Patients with End-Stage Renal Disease Treated by Peritoneal Dialysis Is Intact and Biologically Active
Circulating Fibroblast Growth Factor 23 in Patients with End-Stage Renal Disease Treated by Peritoneal Dialysis Is Intact and Biologically Active
复制标题
DOI：
10.1210/jc.2009-1603
复制
发表时间：
2010-02-01
影响因子：
5.8
通讯作者：
Jueppner, Harald
中科院分区：
文献类型：
--
作者：
Shimada, Takashi;Urakawa, Itaru;Jueppner, Harald
背景：成纤维细胞生长因子23（FGF 23）调节磷稳态和维生素D代谢。循环中的FGF 23水平在可引起佝偻病或骨软化的遗传性和获得性低磷酸盐血症疾病中升高。特别是在慢性肾病（CKD）患者中观察到FGF 23浓度升高，其中FGF 23升高与更快的疾病进展、骨矿化改善、左心室肥大的发展和死亡率增加相关。目的：我们的目的是确定CKD中免疫反应性FGF 23水平的显著升高是否代表完整的生物活性激素的积累，设计：使用基于细胞的Egr-1报告基因测定来定量来自通过腹膜透析治疗的CKD患者的血浆中的生物活性FGF 23;将生物活性FGF 23水平与用免疫计量FGF 23测定测量的那些进行比较，所述免疫计量FGF 23测定检测单独的完整激素或完整激素和C末端片段。成人和儿童患者与终末期肾病腹膜透析治疗参加了在三级转诊center.Results的研究：系列稀释的患者样本显示，在平行运行CHO细胞衍生的重组人FGF 23的生物活性FGF 23的水平。FGF 23生物活性被抗FGF 23抗体抑制。生物活性和免疫反应性FGF 23的水平密切相关，并且用来自透析患者血浆的抗FGF 23抗体免疫沉淀的FGF 23的Western印迹分析仅显示单一突出的蛋白条带，其与重组完整的FGF 23难以区分，没有明确的证据表明FGF 23片段。我们的研究结果为透析患者中几乎所有循环的FGF 23都是完整的和具有生物活性的结论提供了强有力的证据。（临床内分泌代谢杂志95：578-585，2010）
Context: Fibroblast growth factor 23 (FGF23) regulates phosphorus homeostasis and vitamin D metabolism. Circulating FGF23 levels are elevated in inherited and acquired hypophosphatemic disorders that can cause rickets or osteomalacia. Particularly increased concentrations of FGF23 are observed in patients with chronic kidney disease (CKD), in which increased FGF23 is associated with more rapid disease progression, improved bone mineralization, the development of left ventricular hypertrophy, and increased mortality.Objective: Our objective was to determine whether the markedly elevated levels of immunoreactive FGF23 in CKD represent accumulation of intact, biologically active hormone, C-terminal cleavage fragments, or both.Design: Biologically active FGF23 in plasma from CKD patients treated by peritoneal dialysis was quantified using a cell-based Egr-1 reporter assay; bioactive FGF23 levels were compared with those measured with immunometric FGF23 assays detecting either intact hormone alone or intact hormone and C-terminal fragments.Setting and Patients: Adult and pediatric patients with end-stage renal disease treated with peritoneal dialysis participated in the study at a tertiary referral center.Results: Serially diluted patient samples revealed levels of bioactive FGF23 that ran in parallel to CHO cell-derived recombinant human FGF23. FGF23 bioactivity was inhibited by an anti-FGF23 antibody. Levels of bioactive and immunoreactive FGF23 were tightly correlated, and Western blot analysis of FGF23 immunoprecipitated with anti-FGF23 antibodies from plasma of dialysis patients revealed only a single prominent protein band, which was indistinguishable from recombinant intact FGF23, without clear evidence for FGF23 fragments.Conclusions: Our results provide strong evidence for the conclusion that virtually all circulating FGF23 in dialysis patients is intact and biologically active. ( J Clin Endocrinol Metab 95: 578-585, 2010)