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Relationship between circulating FGF23 and total body atherosclerosis 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 Oncology, Radiology and Clinical Immunology, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
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2009 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 24, no 10, 3125-3131 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Fibroblast growth factor-23 (FGF23) is a regulator of mineral metabolism and has been suggested to play a role in vascular calcification in chronic kidney disease (CKD). Data on the association between FGF23 and atherosclerosis, both in CKD and in the community, is limited. METHODS: The total body atherosclerosis score (AS) was determined by a magnetic resonance imaging-based angiography in 306 elderly men and women, representing a subsample of the community-based PIVUS cohort. Subjects were divided into three categories based on AS: AS = 0, low AS and high AS. Serum FGF23 was measured using a two-site monoclonal antibody ELISA. RESULTS: In continuous and multi-category regression models, higher FGF23 was associated with a significant increase in the odds of having a high AS (OR 1.43, CI 1.06-1.92 to OR 3.01, CI 1.52-5.99). This association was stronger in individuals with eGFR <60 mL/min/1.73 m(2) (n = 27), reaching a nearly 6-fold increase in the odds for a high AS in the upper FGF23 tertile (OR 5.64, CI 2.78-11.5). We found weaker support for a relationship between FGF23 and the presence of atherosclerosis as subjects in the highest FGF23 tertile had an increased risk for an AS > 0 in crude models (OR 1.93, CI 1.05-3.55), but this was not statistically significant in adjusted (OR 1.42, CI 0.74-1.72) models. CONCLUSIONS: We provide novel evidence supporting an association between serum FGF23 and total body atherosclerosis in the community. Additional studies are warranted to determine the prospective relationship between FGF23 and atherosclerosis, and whether FGF23 is a modifiable cardiovascular risk factor.

Place, publisher, year, edition, pages
2009. Vol. 24, no 10, 3125-3131 p.
Keyword [en]
atherosclerosis, calcification, chronic kidney disease, FGF23, phosphate
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-120845DOI: 10.1093/ndt/gfp205ISI: 000270219400032PubMedID: 19429932OAI: oai:DiVA.org:uu-120845DiVA: diva2:304011
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)
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Available from: 2010-09-23 Created: 2010-09-06 Last updated: 2011-01-17Bibliographically approved

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Hansen, TomasJohansson, LarsAhlström, Håkan

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