RATIONALE & OBJECTIVE The pathogenesis of disordered mineral metabolism in chronic kidney disease (CKD) is largely informed by cross-sectional studies of humans and longitudinal animal studies. We sought to characterize the longitudinal evolution of disordered mineral metabolism during the course of CKD. STUDY DESIGN Retrospective analysis nested in a cohort study. SETTING & PARTICIPANTS Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had up to 5 serial annual measurements of estimated glomerular filtration rate, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), serum phosphate, and serum calcium and who subsequently reached end-stage kidney disease (ESKD) during follow-up (n = 847). EXPOSURE Years before ESKD. OUTCOMES Serial FGF-23, PTH, serum phosphate, and serum calcium levels. ANALYTICAL APPROACH To assess longitudinal dynamics of disordered mineral metabolism in human CKD, we used "ESKD-anchored longitudinal analyses" to express time as years before ESKD, enabling assessments of mineral metabolites spanning 8 years of CKD progression before ESKD. RESULTS Mean FGF-23 levels increased markedly as time before ESKD decreased, while PTH and phosphate levels increased modestly and calcium levels declined minimally. Compared with other mineral metabolites, FGF-23 levels demonstrated the highest rate of change (velocity: first derivative of the function of concentration over time) and magnitude of acceleration (second derivative). These changes became evident approximately 5 years before ESKD and persisted without deceleration through ESKD onset. Rates of changes in PTH and phosphate levels increased modestly and without marked acceleration around the same time, with modest deceleration immediately before ESKD, when use of active vitamin D and phosphate binders increased. LIMITATIONS Individuals who entered the CRIC Study at early stages of CKD and who did not progress to ESKD were not studied. CONCLUSIONS Among patients with progressive CKD, FGF-23 levels begin to increase 5 years before ESKD and continue to rapidly accelerate until transition to ESKD.

中文翻译：

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CKD 患者矿物质代谢标志物的纵向演变：慢性肾功能不全队列 (CRIC) 研究。

基本原理和目的 慢性肾病 (CKD) 中矿物质代谢紊乱的发病机制主要来自人类的横断面研究和纵向动物研究。我们试图描述 CKD 过程中矿物质代谢紊乱的纵向演变。研究设计 队列研究中嵌套的回顾性分析。设置和参与者 慢性肾功能不全队列 (CRIC) 研究的参与者，他们对估计的肾小球滤过率、成纤维细胞生长因子 23 (FGF-23)、甲状旁腺激素 (PTH)、血清磷酸盐和血清钙进行了多达 5 次连续年度测量随后在随访期间达到终末期肾病 (ESKD) (n = 847)。暴露在 ESKD 之前的几年。结果 连续 FGF-23、PTH、血清磷酸盐和血清钙水平。分析方法为了评估人类 CKD 中矿物质代谢紊乱的纵向动态，我们使用“ESKD 锚定纵向分析”将时间表示为 ESKD 之前的年数，从而能够评估跨越 8 年的 ESKD 之前 CKD 进展的矿物质代谢物。结果平均 FGF-23 水平随着 ESKD 前时间的减少而显着增加，而 PTH 和磷酸盐水平适度增加，钙水平下降最小。与其他矿物代谢物相比，FGF-23 水平显示出最高的变化率（速度：浓度随时间变化的函数的一阶导数）和加速幅度（二阶导数）。这些变化在 ESKD 前大约 5 年变得明显，并且在 ESKD 发作期间持续存在而没有减速。当活性维生素 D 和磷酸盐结合剂的使用增加时，PTH 和磷酸盐水平的变化率适度增加，并且几乎同时没有明显加速，在 ESKD 前即刻适度减速。局限性 未研究在 CKD 早期阶段进入 CRIC 研究且未进展至 ESKD 的个体。结论 在进展性 CKD 患者中，FGF-23 水平在 ESKD 前 5 年开始增加，并继续迅速加速直至过渡到 ESKD。