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Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
2009 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 205, no 2, 385-390 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Subjects with chronic kidney disease (CKD) are at higher risk for cardiovascular (CV) disease than the general population. These patients have elevated circulating levels of FGF23, which predict for increased mortality in CKD patients on hemodialysis. Since CV disease is a major cause of death in CKD, we investigated the association between FGF23 and vascular function. METHODS AND RESULTS: We employed a community-based cohort of subjects aged 70, the PIVUS study (n=967), to investigate the relation between serum FGF23, endothelium function and arterial stiffness. Higher FGF23 was weakly associated with both impaired endothelium-dependent (beta=-0.08, p<0.05) and endothelium-independent (beta=-0.08, p<0.01) vasodilation. The association was stronger in subjects with eGFR> or =90mL/min/1.73m(2) (beta=-0.19 and beta=-0.22, respectively, p<0.001). In addition, higher FGF23 was associated with increased arterial stiffness exclusively in subjects with an age-adjusted impaired renal function (eGFR<60mL/min/1.73m(2)) (beta=0.26, p<0.001). All associations were independent of gender, biochemical covariates and established CV risk factors. CONCLUSIONS: Higher serum FGF23 levels, even within the normal range, are independently associated with impaired vasoreactivity and increased arterial stiffness in the community. Additional studies are required to determine possible direct vascular effects of FGF23 and whether FGF23 is a modifiable CV risk factor.

Place, publisher, year, edition, pages
2009. Vol. 205, no 2, 385-390 p.
Keyword [en]
Fibroblast growth factor-23, FGF23, Klotho, Vascular function, Atherosclerosis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-120846DOI: 10.1016/j.atherosclerosis.2009.01.001ISI: 000269289500011PubMedID: 19181315OAI: oai:DiVA.org:uu-120846DiVA: diva2:304013
Available from: 2010-03-16 Created: 2010-03-16 Last updated: 2017-12-12Bibliographically approved
In thesis
1. The role of fibroblast growth factor-23 in chronic kidney disease-mineral and bone disorder
Open this publication in new window or tab >>The role of fibroblast growth factor-23 in chronic kidney disease-mineral and bone disorder
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Fibroblast growth factor-23 (FGF23) was initially identified as the causative factor of autosomal dominant hypophosphatemic rickets. Further studies confirmed that FGF23 is predominantly expressed in the osteocytes and osteoblasts of bone and that circulating FGF23 acts on the kidney to inhibit renal phosphate reabsorption and 1,25(OH)2D3 hydroxylation.

With the progression of chronic kidney disease (CKD), the kidneys become insufficient to maintain a normal systemic mineral homeostasis, resulting in various abnormalities of bone and mineral metabolism, generally referred to as Chronic Kidney Disease – Mineral and Bone Disorders (CKD-MBD). FGF23 increases early in the course of CKD in order to maintain normal serum phosphate levels; long before a significant increase in serum phosphate can be detected. Recent studies suggest that increased FGF23 levels are associated with progression of CKD, mortality, and the development of refractory secondary hyperparathyroidism. Because FGF23 is the very earliest marker of CKD-MBD, it is of particular interest to evaluate the relation between FGF23 and CKD-MBD abnormalities, in the setting of early CKD and also in individuals with normal renal function.

In the present work, we show that FGF23 is linked to several dynamic measurements of vascular function, including endothelial dysfunction, arterial stiffness, and atherosclerosis. FGF23 is also positively associated with left ventricular mass index and an increased risk of having left ventricular hypertrophy. All associations were independent of serum phosphate and were strengthened in subjects with diminished renal function. Furthermore, we found significant evidence for an association between higher FGF23 and increased fat mass and dyslipidemia, which could represent a novel pathway linking FGF23 to cardiovascular disease. Finally, we show that FGF23 is a significant predictor of future fracture risk.

Although these associations could be reflecting the increased risk associated with hyperphosphatemia and calcitriol deficiency, current evidence points towards FGF23 being more than an innocent bystander. At the very least, FGF23 holds promise of being a bio-marker of cardiovascular status and phosphate-related toxicity both in CKD and in the general population, and might be a therapeutic target that could improve the fatal prognosis in CKD patients.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 83 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 594
Keyword
FGF23, FGF-23, CKD, CKD-MBD, cardiovascular disease, vascular function, atherosclerosis, hypertrophy, LVMI, LVH, fractures, bone, fat mass, obesity, apolipoproteins, cholesterol, lipids
National Category
Urology and Nephrology Cardiac and Cardiovascular Systems
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-130339 (URN)978-91-554-7883-4 (ISBN)
Public defence
2010-10-16, Grönwallsalen, Akademiska sjukhuset, ingång 70, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2010-09-23 Created: 2010-09-06 Last updated: 2011-01-17Bibliographically approved

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