Fibroblast growth factor 23 and new-onset chronic kidney disease in the general population: The Prevention of Renal and Vascular Endstage Disease (PREVEND) study

Abstract

Background. Fibroblast growth factor 23 (FGF23), a phosphate-regulating hormone that increases early in the course of chronic kidney disease (CKD), is associated with disease progression in patients with established CKD. Here we aimed to investigate the association between plasma FGF23 and new-onset CKD in the general population. Methods. We included 5253 individuals without CKD who participated in the Prevention of Renal and Vascular Endstage Disease study, a prospective, population-based cohort. Multivariable Cox regression was used to study the association of plasma C-terminal FGF23 with new-onset CKD, defined as a combined endpoint of estimated glomerular filtration rate (eGFR) <60mL/min/ 1.73m2, urinary 24-h albumin excretion (UAE) >30mg/24 h or both, or with all-cause mortality. Results. The median baseline FGF23 was 68 [interquartile range (IQR) 56-85]RU/mL, eGFR was 95613mL/min/ 1.73m2 and UAE was 7.8 (IQR 5.8-11.5) mg/24 h. After follow-up of 7.5 (IQR 7.2-8.0) years, 586 participants developed CKD and 214 participants died. A higher FGF23 level was associated with new-onset CKD, independent of risk factors for kidney disease and parameters of bone and mineral homoeostasis {fully adjusted hazard ratio (HR) 1.25 [95% confidence interval (CI) 1.10-1.44] per doubling of FGF23; P=0.001}. In secondary analyses, FGF23 was independently associated with new-onset eGFR <60mL/min/1.73m2 [adjusted HR 1.28 (95% CI 1.00- 1.62); P=0.048] or with UAE >30mg/24 h [adjusted HR 1.24 (95% CI 1.06-1.45); P=0.01] individually. A higher FGF23 level was also associated with an increased risk of all-cause mortality [fully adjusted HR 1.30 (95% CI 1.03-1.63); P=0.03]. Conclusions. High FGF23 levels are associated with an increased risk of new-onset CKD and all-cause mortality in this prospective population-based cohort, independent of established CKD risk factors.