Fibroblast growth factor 23 as a risk factor for cardiovascular events and mortality in patients in the EVOLVE trial

Abstract

Introduction High mortality rates in patients with chronic kidney disease‐mineral and bone disorder (CKD‐MBD) receiving maintenance hemodialysis are largely due to cardiovascular (CV) events. Methods We evaluated associations between MBD parameters, fibroblast growth factor 23 (FGF23) concentrations, and clinically adjudicated CV events from the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial. Patients enrolled in EVOLVE, who had not experienced any study endpoints between randomization and week 20 with evaluable baseline and week 20 values for key laboratory parameters (parathyroid hormone, calcium, phosphate, and FGF23), were assessed. We used adjusted Cox proportional hazards regression models to estimate relative risk of outcomes (primary composite, all‐cause mortality, and CV events) based on FGF23 and MBD parameters. Laboratory values were modeled with linear terms and using natural cubic splines with two degrees of freedom. Findings For the primary endpoint, patients assessed (N = 2309) were followed up over a mean duration of 3.1 years, during which 1037 CV events (497 deaths, 540 nonfatal events) occurred. Adjusted models showed an association between FGF23 and the risk of CV events. Hazard ratio per log unit of FGF23 at week 20 was 1.09 [95% CI: 1.03–1.16], and the hazard ratio per log unit change in FGF23 from week 0 to week 20 was 1.09 [95% CI: 1.00–1.17]. Discussion Our data highlight FGF23 as an independent CV risk factor and potential biomarker and therapeutic target for patients with CKD‐MBD receiving maintenance hemodialysis.

Plasma Xanthine Oxidoreductase Activity Associated with Glycemic Control in Patients with Pre-Dialysis Chronic Kidney Disease

“…Fibroblastic growth factor 23 (FGF-23), a bone-derived hormone, has a physiological role in regulation of phosphate, 1,25-dihydroxyvitamin D, and PTH [25-28]. Elevated FGF-23 levels have been shown to be associated with CVD events in patients with CKD [29, 30]. It is conceivable that FGF-23 is a potential biomarker that may be useful to improve current clinical practice related to management of CKD mineral and bone disorder (CKD-MBD) [31-33].…”

Fibroblast growth factor 23 is pumping iron: C-terminal-fibroblast growth factor 23 cleaved peptide and its function in iron metabolism

“…Multiple studies have suggested that circulating iFGF23 might be a potent contributor to iron deficiency and consequent anemia in mice and humans [39,44–48]. We show that animals lacking Fgf23 in osteoblasts and osteocytes (Dmp1-Cre Fgf23 conditional-knockout mice) fail to secrete FGF23 in response to inflammatory stimuli such as IL-1β.…”

Efficacy and Safety of Upacicalcet in Hemodialysis Patients with Secondary Hyperparathyroidism

“…Elevated FGF23 concentrations are associated with cardiovascular events, infections, and death. 24–27 Cinacalcet treatment was reported to reduce serum FGF23 concentrations, which was associated with the prevention of cardiovascular mortality and heart failure. 28 In our study, the median changes in serum FGF23 after 24 weeks of upacicalcet and placebo treatment were 60% and 3%, respectively.…”