Medical Sciences Postgraduate Program, Department of Clinical Medicine, Universidade Federal do Ceará, Avenida Abolição, 4043 Ap 1203, Fortaleza, Ceará, CEP 60165-082, Brazil.
Medical Sciences Postgraduate Program, Universidade de Fortaleza-UNIFOR, Fortaleza, Ceara, Brazil.
J Transl Med. 2019 Apr 11;17(1):121. doi: 10.1186/s12967-019-1875-6.
Fibroblast growth factor 23 (FGF23) and endothelium-related biomarkers have been related to AKI in critically-ill patients. Also, FGF23 is associated with endothelial dysfunction. In this study, we investigated if elevated FGF23 association with severe AKI is mediated by several endothelial/glycocalyx-related biomarkers.
Prospective cohort study with critically-ill patients. Blood samples were collected within the first 24 h after ICU admission. Severe AKI (defined according to KDIGO stage 2/3) was the analyzed outcome.
265 patients were enrolled and 82 (30.9%) developed severe AKI-defined according to KDIGO stage 2/3. Blood samples to biomarkers measurement were collected within the first 24 h after ICU admission. After adjustment for several variables, FGF23, vascular cell adhesion protein 1 (VCAM-1), angiopoietin 2 (AGPT2), syndecan-1 and intercellular adhesion molecule-1 (ICAM-1) were associated with severe AKI. The individual indirect effects of VCAM-1, AGPT2 and syndecan-1 explained 23%, 31%, and 32% of the total observed effect of FGF23 on severe AKI, respectively. ICAM-1 showed no statistically significant mediation. When all three endothelium-related biomarkers were included in a directed acyclic graph (DAG), the Bayesian network learning suggested the following causal association pathway FGF-23 → syndecan-1 → VCAM-1 → AGPT2 → severe AKI.
The association between FGF23 and AKI are mediated by endothelium-related biomarkers, mainly VCAM-1, AGPT2 and syndecan-1. Moreover, the statistical models show that syndecan-1, a biomarker of endothelial glycocalyx dysfunction, seems to be the initial mediator between FGF23 and severe AKI.
成纤维细胞生长因子 23（FGF23）和与内皮细胞相关的生物标志物与危重病患者的急性肾损伤（AKI）有关。此外，FGF23 与内皮功能障碍有关。在这项研究中，我们研究了升高的 FGF23 是否通过几种与内皮细胞/糖萼相关的生物标志物与严重 AKI 相关。
对危重病患者进行前瞻性队列研究。血液样本在 ICU 入院后 24 小时内采集。严重 AKI（根据 KDIGO 第 2/3 阶段定义）是分析结果。
共纳入 265 例患者，其中 82 例（30.9%）发生了严重 AKI（根据 KDIGO 第 2/3 阶段定义）。生物标志物测量的血液样本是在 ICU 入院后 24 小时内采集的。调整了几个变量后，FGF23、血管细胞黏附蛋白 1（VCAM-1）、血管生成素 2（AGPT2）、硫酸乙酰肝素蛋白聚糖 1（syndecan-1）和细胞间黏附分子 1（ICAM-1）与严重 AKI 相关。VCAM-1、AGPT2 和 syndecan-1 的个体间接效应分别解释了 FGF23 对严重 AKI 的总观察效应的 23%、31%和 32%。ICAM-1 没有显示出统计学上的显著中介作用。当将所有三种与内皮相关的生物标志物纳入有向无环图（DAG）中时，贝叶斯网络学习表明了以下因果关联途径：FGF-23→syndecan-1→VCAM-1→AGPT2→严重 AKI。
FGF23 与 AKI 之间的关联是由与内皮相关的生物标志物介导的，主要是 VCAM-1、AGPT2 和 syndecan-1。此外，统计模型表明，内皮糖萼功能障碍的生物标志物 syndecan-1 似乎是 FGF23 与严重 AKI 之间的初始介导物。
