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

Maarten A. De Jong, Michele F. Eisenga, Adriana J. van Ballegooijen, Joline W.J. Beulens, Marc G. Vervloet, Gerjan Navis, Ron T. Gansevoort, Stephan J.L. Bakker, Martin H. De Borst

Research output: Contribution to JournalArticleAcademicpeer-review

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. Multi-variable 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) <60 mL/min/ 1.73 m2, urinary 24-h albumin excretion (UAE) >30 mg/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 95 ± 13 mL/min/1.73 m2 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 <60 mL/min/1.73 m2 [adjusted HR 1.28 (95% CI 1.00-1.62); P = 0.048] or with UAE >30 mg/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.

Original languageEnglish
Pages (from-to)121-128
Number of pages8
JournalNephrology Dialysis Transplantation
Volume36
Issue number1
Early online date3 Mar 2020
DOIs
Publication statusPublished - Jan 2021

Funding

This study has been supported by the Dutch Kidney Foundation (grants CP1601 and 17OKG18). received research support from Amgen and Fresenius Medical Care (all outside the submitted work). M.H.d.B. has consultancy agreements with Amgen, AstraZeneca, Bayer, Kyowa Kirin, Pharmacosmos, Vifor Fresenius Medical Care Renal Pharma and Sanofi Genzyme and has received grant support from Amgen and Sanofi Genzyme (all outside the submitted work).

FundersFunder number
Amgen
AstraZeneca
Bayer
Sanofi Genzyme
NierstichtingCP1601, 17OKG18
Kyowa Hakko Kirin

    Keywords

    • chronic kidney disease
    • epidemiology
    • fibroblast growth factor 23
    • general population
    • mortality

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