Fibroblast growth factor 23, endothelium biomarkers and acute kidney injury in critically-ill patients

• Main Authors: Fernanda Macedo de Oliveira Neves, Camila Barbosa Araújo, Daniele Ferreira de Freitas, Bianca Fernandes Távora Arruda, Leonardo José Monteiro de Macêdo Filho, Vivian Brito Salles, Gdayllon Cavalcante Meneses, Alice Maria Costa Martins, Alexandre Braga Libório
• Format: Article
• Language: English
• Published: BMC 2019-04-01
• Series: Journal of Translational Medicine
• Subjects: Acute kidney injury; Endothelium; Fibroblast growth factor 23; Mediation; ICU
• Online Access: http://link.springer.com/article/10.1186/s12967-019-1875-6

Abstract Background 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. Methods 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. Results 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. Conclusions 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.