RATIONALE & OBJECTIVE Studies using a single measurement of fibroblast growth factor 23 (FGF-23) suggest that elevated FGF-23 levels are associated with increased risk for requirement for kidney replacement therapy (KRT) in patients with chronic kidney disease. However, the data do not account for changes in FGF-23 levels as kidney disease progresses. STUDY DESIGN Case-cohort study. SETTING & PARTICIPANTS To evaluate the association between serial FGF-23 levels and risk for requiring KRT, our primary analysis included 1,597 individuals in the Chronic Renal Insufficiency Cohort Study who had up to 5 annual measurements of carboxy-terminal FGF-23. There were 1,135 randomly selected individuals, of whom 266 initiated KRT, and 462 individuals who initiated KRT outside the random subcohort. EXPOSURE Serial FGF-23 measurements and FGF-23 trajectory group membership. OUTCOMES Incident KRT. ANALYTICAL APPROACH To handle time-dependent confounding, our primary analysis of time-updated FGF-23 levels used time-varying inverse probability weighting in a discrete time failure model. To compare our results with prior data, we used baseline and time-updated FGF-23 values in weighted Cox regression models. To examine the association of FGF-23 trajectory subgroups with risk for incident KRT, we used weighted Cox models with FGF-23 trajectory groups derived from group-based trajectory modeling as the exposure. RESULTS In our primary analysis, the HR for the KRT outcome per 1 SD increase in the mean of natural log-transformed (ln)FGF-23 in the past was 1.94 (95% CI, 1.51-2.49). In weighted Cox models using baseline and time-updated values, elevated FGF-23 level was associated with increased risk for incident KRT (HRs per 1 SD ln[FGF-23] of 1.18 [95% CI, 1.02-1.37] for baseline and 1.66 [95% CI, 1.49-1.86] for time-updated). Membership in the slowly and rapidly increasing FGF-23 trajectory groups was associated with ∼3- and ∼21-fold higher risk for incident KRT compared to membership in the stable FGF-23 trajectory group. LIMITATIONS Residual confounding and lack of intact FGF-23 values. CONCLUSIONS Increasing FGF-23 levels are independently associated with increased risk for incident KRT.

中文翻译：

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连续成纤维细胞生长因子23的测定和肾脏替代疗法的需求风险：CRIC（慢性肾功能不全队列）研究。

理由和目的使用单一测量的成纤维细胞生长因子23（FGF-23）的研究表明，慢性肾脏病患者中FGF-23水平升高与肾脏替代疗法（KRT）需求风险增加有关。但是，该数据并未说明随着肾脏疾病的进展，FGF-23水平的变化。研究设计案例研究。地点和参与者为了评估FGF-23系列水平与需要KRT的风险之间的关系，我们的主要分析包括1597例慢性肾功能不全队列研究中的受试者，这些受试者每年进行5次羧基末端FGF-23的测定。共有1135个随机选择的个体，其中266个发起了KRT，462个个体在随机亚组之外发起了KRT。暴露连续FGF-23测量和FGF-23轨迹组成员身份。结果事故KRT。分析方法为了处理时间相关的混杂因素，我们对时间更新的FGF-23水平的主要分析在离散时间故障模型中使用了时变逆概率加权。为了将我们的结果与先前的数据进行比较，我们在加权Cox回归模型中使用了基线和时间更新的FGF-23值。为了检查FGF-23轨迹子组与发生KRT的风险之间的关系，我们使用加权Cox模型与源自基于组轨迹模型的FGF-23轨迹组作为暴露量。结果在我们的主要分析中，过去自然对数转化的（ln）FGF-23的平均值每增加1 SD，KRT结果的HR为1.94（95％CI，1.51-2.49）。在使用基准值和时间更新值的加权Cox模型中，FGF-23水平升高与发生KRT的风险增加相关（基线时每1 SD ln [FGF-23]的HRs为1.18 [95％CI，1.02-1.37]，时间为1.66 [95％CI，1.49-1.86] -更新）。与稳定的FGF-23轨迹组的成员相比，缓慢而迅速增长的FGF-23轨迹组的成员与发生KRT的风险分别高约3倍和约21倍。局限性残留混杂物，缺乏完整的FGF-23值。结论FGF-23水平的增加与发生KRT的风险增加独立相关。与稳定的FGF-23轨迹组的成员相比，缓慢而迅速增加的FGF-23轨迹组的成员与发生KRT的风险分别高出约3倍和21倍。局限性残留混杂物，缺乏完整的FGF-23值。结论FGF-23水平的增加与发生KRT的风险增加独立相关。与稳定的FGF-23轨迹组的成员相比，缓慢而迅速增长的FGF-23轨迹组的成员与发生KRT的风险分别高约3倍和约21倍。局限性残留混杂物，缺乏完整的FGF-23值。结论FGF-23水平的增加与发生KRT的风险增加独立相关。