Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency

Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency
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DOI:
10.1053/j.ajkd.2004.04.029
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发表时间:
2004-08-01
影响因子:
13.2
通讯作者:
Fukagawa, M
Fukagawa, M
中科院分区:
医学1区
文献类型:
--
作者:
Shigematsu, T;Kazama, JJ;Fukagawa, M

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背景 成纤维细胞生长因子 23 (FGF-23) 是最近发现的一种多肽,可促进肾磷酸盐排泄并降低血清 1,25-二羟基维生素 D-3 (1,25D) 水平。终末期肾衰竭患者的血清 FGF-23 水平异常升高。方法:从 62 名透析前患者(年龄,51.3 +/- 14.0 岁;范围,类似于 18 至 76 岁;32 名男性,30 名女性)获取血液和尿液样本。血清 FGF-23 水平通过夹心酶联免疫吸附测定系统测定,使用 2 种单克隆抗体,迄今为止,该系统无法检测源自已鉴定的内部切割位点的生物无活性 N 端和 C 端片段。结果:血清FGF-23水平随着肌酐清除率(Ccr)的降低而升高。完整甲状旁腺激素 (PTH) 和 1-84 PTH 水平均与 FGF-23 水平密切相关 (r(2) = 0.857;r(2) = 0.860)。发现 FGF-23 和 1,25D 血清浓度之间存在负相关(r(2) = 0.255)。磷酸盐的最大肾小管重吸收率与血清 FGF-23 浓度呈负相关(r(2) = 0.460)。然而,Ccr 低于 30 mL/min 的患者每日尿磷酸盐排泄量显着减少(
Background Fibroblast growth factor 23 (FGF-23) is a recently identified polypeptide that promotes renal phosphate excretion and decreases serum 1,25-dihydroxyvitamin D-3 (1,25D) levels. Serum FGF-23 levels are extraordinarily elevated in patients with end-stage renal failure. Methods: Blood and urine samples were obtained from 62 predialysis patients (age, 51.3 +/- 14.0 years; range, similar to18 to 76 years; 32 men, 30 women). Serum FGF-23 levels were determined by means of a sandwich enzyme-linked immunosorbent assay system using 2 kinds of monoclonal antibodies that does not detect biologically inactive N-terminal and C-terminal fragments derived from an identified internal cleavage site to date. Results: Serum FGF-23 levels increased with the decrease in creatinine clearance (Ccr). Both intact parathyroid hormone (PTH) and 1-84 PTH levels correlated closely with FGF-23 levels (r(2) = 0.857; r(2) = 0.860). A negative correlation between serum concentrations of FGF-23 and 1,25D (r(2) = 0.255) was found. The maximum tubular reabsorptive rate of phosphate correlated negatively with serum FGF-23 concentrations (r(2) = 0.460). However, the amount of daily urinary phosphate excretion was significantly less in patients with a Ccr less than 30 mL/min (