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Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population
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. (Clinical pharmacogenetics and osteoporosis)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2009 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 207, no 2, 546-551 p.Article in journal (Refereed) Published
Abstract [en]

Fibroblast growth factor-23 (FGF23) is a hormonal regulator of circulating phosphate and vitamin D levels. Serum FGF23 is elevated in chronic kidney disease (CKD) and is a prognostic marker of poor outcomes, such as faster CKD progression and increased mortality in hemodialysis patients. Despite the high prevalence of cardiovascular disease in CKD, the relation between circulating FGF23 and cardiovascular risk factors, both in CKD and in the community, has not been studied in detail. We evaluated the relation between FGF23, left ventricular mass index (LVMI), hypertrophy (LVH) and LV geometry, employing the community-based PIVUS cohort. In total, 795 Swedish men and women aged 70 were included of which 164 had an age-adjusted diminished renal function (estimated glomerular filtration rate<60mL/min/1.73m(2)). FGF23 was positively associated with LVMI (beta=0.11, CI 0.01-0.18), with increased odds for the presence of LVH (OR 1.28, CI 1.09-1.51) and for concentric hypertrophy (OR 1.45, CI 1.19-1.77) in the whole population. All associations were stronger in subjects with eGFR<60mL/min/1.73m(2) (beta=0.30, CI 0.15-0.46 for LVMI; OR 1.86, CI 1.30-2.67 for the presence of LVH; OR 1.83, CI 1.17-2.85 and OR 1.87, CI 1.08-3.22 for concentric and eccentric hypertrophy, respectively). The results were essentially unaltered in multivariate models. In summary, elevated serum FGF23 levels, even within the normal range, are associated with increased LVMI and increased risk for the presence of LVH in elderly subjects. Additional longitudinal studies that evaluate the predictive power of FGF23 and whether FGF23 has additional clinical applications are needed.

Place, publisher, year, edition, pages
2009. Vol. 207, no 2, 546-551 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-130327DOI: 10.1016/j.atherosclerosis.2009.05.013ISI: 000273566700042PubMedID: 19524924OAI: oai:DiVA.org:uu-130327DiVA: diva2:349303
Available from: 2010-09-06 Created: 2010-09-06 Last updated: 2011-01-11Bibliographically 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.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 594
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
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)
Available from: 2010-09-23 Created: 2010-09-06 Last updated: 2011-01-17Bibliographically approved

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