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Oncogenic osteomalacia illustrating the effects of fibroblast factor 23 on phospahte homeostasis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
Katholieke Universiteit, Leuven.
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2012 (English)In: Clinical Kidney Journal, ISSN 2048-8505, Vol. 5, no 3, 240-243 p.Article in journal (Refereed) Published
Abstract [en]

In oncogenic osteomalacia (OOM), fibroblast growth factor 23 (FGF23) induces renal phosphate wasting and inhibits the appropriate increase of calcitriol. A patient suffering from OOM is described. Serum calcium, phosphate, biointact parathyroid hormone and intact FGF23 as well as the calcitriol and 24,25-vitamin D levels were measured before and after tumour removal. The clinical approach to a patient with hypophosphataemia is discussed and the changes in mineral metabolism after removal of a FGF23-producing tumour are described.

Place, publisher, year, edition, pages
2012. Vol. 5, no 3, 240-243 p.
National Category
Urology and Nephrology
URN: urn:nbn:se:uu:diva-188144DOI: 10.1093/ckj/sfs031OAI: oai:DiVA.org:uu-188144DiVA: diva2:576365

Clinical report

Available from: 2012-12-12 Created: 2012-12-12 Last updated: 2013-02-21Bibliographically approved
In thesis
1. Aspects of Fibroblast Growth Factor 23 in Mild to Moderate Renal Dysfunction
Open this publication in new window or tab >>Aspects of Fibroblast Growth Factor 23 in Mild to Moderate Renal Dysfunction
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Disturbances in mineral metabolism contribute to vascular calcification and mortality risk in chronic kidney disease (CKD). Serum levels of fibroblast growth factor (FGF)23, a bone derived, phosphaturic peptide, are associated with cardiovascular mortality in CKD. Membrane bound klotho(KL) is an obligate co receptor for FGF23 signaling in the kidney. To study aspects of FGF23 in mild to moderate impairment of renal function we have analyzed FGF23, estimated glomerular filtration rate (eGFR), parathyroid hormone(PTH), 1,25 (OH)2 vitamin D (1,25D), calcium and phosphate in one patient with a FGF23 producing tumor, before and after tumor removal (study 1), in 72 CKD patients with varying degree of renal dysfunction (study 2), in 9 healthy kidney donors, before and after nephrectomy (study 3). We also analyzed FGF23 (study 4), and performed genotyping of 27 single nucleotide polymorphisms (SNP) of the KL gene (study 5) in 2838 elderly Swedish men (MrOs study) and examined the association with mortality.

FGF23 normalizes in 30-45 minutes after removal of a FGF23 producing tumor (study 1). 1,25D increases in hours and remains elevated months, even when the other parameters have normalized. FGF23 increase early in CKD, initially slowly, in correlation with PTH, but exponentially when hyperphosphatemia ensues (study 2). After unilateral nephrectomy (study 3) mineral homeostasis remain stable, initially due to a rise in PTH and later to an increase in FGF23.

FGF23 levels are not correlated with mortality in elderly men after adjustment for eGFR, but with mortality due to cardiovascular disease, even in persons with normal eGFR (study 4). Polymorphism of the KL gene do not correlate with increased mortality risk in elderly men (study 5), but there is a modulating effect on FGF23 levels.

FGF23 is of importance in maintaining phosphate homeostasis as renal function declines. It is co regulated with PTH until advanced renal dysfunction, and adjust the 1,25D to the actual GFR. FGF23 is associated with cardiovascular mortality. Further studies are needed to determine the mechanism, and if reduction of FGF23 by reducing phosphate intake may be beneficial even in persons with mild to moderate renal function.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 59 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 852
FGF23, phosphate, mineral metabolism, elderly, mortality
National Category
Urology and Nephrology
Research subject
urn:nbn:se:uu:diva-188233 (URN)978-91-554-8564-1 (ISBN)
Public defence
2013-02-08, Enghoffsalen, Akademiska Sjukhuset , ingång 50, plan1, Uppsala, 13:00 (English)
Available from: 2013-01-17 Created: 2012-12-14 Last updated: 2013-04-02Bibliographically approved

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Westerberg, Per-AntonLinde, TorbjörnLjunggren, Östen
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