Leaf David E, Jacob Kirolos A, Srivastava Anand, Chen Margaret E, Christov Marta, Jüppner Harald, Sabbisetti Venkata S, Martin Aline, Wolf Myles, Waikar Sushrut S
Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts;
Department of Cardiothoracic Surgery, University Medical Center, Utrecht, Utrecht, The Netherlands.
J Am Soc Nephrol. 2017 Jun;28(6):1877-1885. doi: 10.1681/ASN.2016080836. Epub 2016 Dec 27.
Elevated plasma levels of the osteocyte-derived hormone fibroblast growth factor 23 (FGF23) have emerged as a powerful biomarker of cardiovascular disease and death in patients with CKD. Whether elevated urinary or plasma FGF23 levels are prospectively associated with AKI and death in critically ill patients is unknown. We therefore conducted a prospective cohort study of 350 critically ill patients admitted to intensive care units at an academic medical center to investigate whether higher urinary FGF23 levels associate with the composite end point of AKI or in-hospital mortality (AKI/death). We measured urinary FGF23 levels within 24 hours of admission to the intensive care unit. In a subcohort (=131) we also measured plasma levels of FGF23, calcium, phosphate, parathyroid hormone, and vitamin D metabolites. Urinary and plasma FGF23 levels, but not other mineral metabolites, significantly associated with AKI/death. In multivariate analyses, patients in the highest compared with the lowest quartile of urinary FGF23 had a 3.9 greater odds (95% confidence interval, 1.6 to 9.5) of AKI/death. Higher urinary FGF23 levels also independently associated with greater hospital, 90-day, and 1-year mortality; longer length of stay; and several other important adverse outcomes. In conclusion, elevated FGF23 levels measured in the urine or plasma may be a promising novel biomarker of AKI, death, and other adverse outcomes in critically ill patients.
骨细胞衍生的成纤维细胞生长因子23（FGF23）的血浆水平升高已成为慢性肾脏病患者心血管疾病和死亡的有力生物标志物。在危重症患者中，尿或血浆FGF23水平升高是否与急性肾损伤（AKI）及死亡存在前瞻性关联尚不清楚。因此，我们对一家学术医疗中心重症监护病房收治的350例危重症患者进行了一项前瞻性队列研究，以调查较高的尿FGF23水平是否与AKI或院内死亡（AKI/死亡）的复合终点相关。我们在患者入住重症监护病房的24小时内测量了尿FGF23水平。在一个亚队列（n = 131）中，我们还测量了血浆中FGF23、钙、磷、甲状旁腺激素和维生素D代谢产物的水平。尿和血浆FGF23水平而非其他矿物质代谢产物与AKI/死亡显著相关。在多变量分析中，尿FGF23处于最高四分位数的患者与最低四分位数的患者相比，发生AKI/死亡的几率高3.9倍（95%置信区间为1.6至9.5）。较高的尿FGF23水平还与更高的住院死亡率、90天死亡率和1年死亡率独立相关；住院时间更长；以及其他几个重要的不良结局。总之，尿或血浆中FGF23水平升高可能是危重症患者AKI、死亡及其他不良结局的一种很有前景的新型生物标志物。
