Department of Renal Medicine, Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Level 2, 5 Arnold Street, Box Hill, 3128 Victoria, Australia.
J Clin Endocrinol Metab. 2012 Sep;97(9):3357-65. doi: 10.1210/jc.2012-1811. Epub 2012 Jun 11.
FGF23 measurement may have a role in the management of patients with chronic kidney disease (CKD).
Our objective was to study the biological variability of plasma intact FGF23 (iFGF23) and C-terminal FGF23 (cFGF23) concentrations.
Plasma samples were taken from 12 healthy adults at multiple time points on 2 consecutive days to assess diurnal variability of FGF23 concentrations. Early-morning fasting and nonfasting samples were also taken over a 6-wk period to estimate components of biological variation. Samples from 170 volunteers were used to define reference intervals. FGF23 concentrations were measured by commercial ELISA. Western blotting was used to analyze FGF23 species from the plasma of healthy adults and patients with predialysis CKD and those undergoing dialysis.
A total of 180 healthy adults and 18 adults with stage 3-5D CKD participated in this study at a hospital research unit.
Estimates were made of the biological variability of plasma FGF23 concentrations.
iFGF23, but not cFGF23, showed significant diurnal variation. cFGF23 had a significantly lower intra-individual variation than iFGF23 (8.3 vs. 18.3%) but higher inter-individual variation than iFGF23 (28.9 vs. 19.2%). Fourteen samples would be needed to estimate an individual's homeostatic set point (within 10%) for iFGF23 compared with only three samples for cFGF23. Using Western blotting, C-terminal FGF23 fragments were detected in the plasma of individuals with normal renal function and at all stages of renal disease. The percent cFGF23 was significantly higher in those without renal impairment (P < 0.001) and was positively correlated with plasma phosphate concentration in those with normal renal function.
The high intra-individual biological variability of iFGF23 may limit its clinical use as a diagnostic or management tool. Risk-related thresholds may be more appropriate for clinical decision making based on cFGF23 measurements than conventional reference intervals. FGF23 cleavage pathways may be an important natural regulatory mechanism for phosphate control.
成纤维细胞生长因子 23（FGF23）的检测可能在慢性肾脏病（CKD）患者的管理中发挥作用。
本研究旨在研究血浆完整 FGF23（iFGF23）和 C 端 FGF23（cFGF23）浓度的生物学变异性。
连续两天，在 12 名健康成年人的多个时间点采集血浆样本，以评估 FGF23 浓度的日间变异性。还在 6 周的时间内采集清晨空腹和非空腹样本，以估计生物学变异的组成部分。来自 170 名志愿者的样本用于定义参考区间。使用商业 ELISA 测量 FGF23 浓度。使用 Western blot 分析健康成年人和透析前 CKD 阶段 3-5D 患者的血浆中 FGF23 种类。
这项研究在医院研究单位共纳入了 180 名健康成年人和 18 名 CKD 阶段 3-5D 的成年人。
估计血浆 FGF23 浓度的生物学变异性。
iFGF23，但不是 cFGF23，表现出明显的昼夜变化。cFGF23 的个体内变异性明显低于 iFGF23（8.3%比 18.3%），但个体间变异性高于 iFGF23（28.9%比 19.2%）。与 cFGF23 相比，需要 14 个样本才能估计 iFGF23 的个体内稳态设定点（10%以内），而仅需要 3 个样本即可估计 cFGF23 的个体内稳态设定点。使用 Western blot 法，在肾功能正常和所有肾脏疾病阶段的个体的血浆中均检测到 C 端 FGF23 片段。在没有肾功能损害的个体中，cFGF23 的百分比显著升高（P < 0.001），并且在肾功能正常的个体中与血浆磷酸盐浓度呈正相关。
iFGF23 的个体内生物学变异性高可能限制其作为诊断或管理工具的临床应用。基于 cFGF23 测量的临床决策可能更适合使用风险相关阈值，而不是传统的参考区间。FGF23 裂解途径可能是磷酸盐控制的重要天然调节机制。
