Fibroblast Growth Factor 23

Fibroblast Growth Factor 23 describes how FGF23 was initially identified as a bone-derived factor targeting the kidney. As such, sections in this comprehensive book cover exciting research that shows that different FGF23 effects require distinct signaling receptors and mediators that differ among target tissues, cover FGF23 initially identified as a bone-derived factor targeting the kidney, look at FGF23 as a regulator of phosphate metabolism and beyond, and cover research on novel concepts of FGF receptor signaling. Additional sections cover biochemistry, pharmacology and nephrology, making this book an ideal reference source on FGF23. Provides a comprehensive collection of chapters on the diversity of FGF23's actions Highlights truly translational topics, from molecular signaling to physiology and mechanism of disease, discussing cell culture and animal models to study FGF23 Describes FGF23’s potential in the clinical setting as a biomarker or even drug target Presents leaders in the field who cover a wide spectrum of research backgrounds and expertise, including clinical and basic scientists who specialize in diseases, endocrinology, genetics, protein biochemistry, cell biology and physiology

Background and aim: Fibroblast Growth Factor-23 (FGF-23) has been shown to be elevated in early stage CKD. The primary stimulus for this increase remains unclear and it is still unknown whether the increase in FGF-23 has a biological effect on bone metabolism and vascular calcification. The aim of the study was to investigate in a cross - sectional design (1) the factors which are associated with elevated serum FGF-23 (2) the association between FGF-23 and bone metabolism (3) the association between FGF-23 and vascular stiffness in CKD. -- Method: One hundred and forty five ambulant predialysis patients (74 M, 71 F) aged (mean [SD]) 53 [14] years with CKD 1-4 were studied. Routine biochemical parameters were measured. In addition C - reactive protein (CRP), 1,25 dihydroxyvitamin D, FGF-23, bone turnover markers (bone alkaline phosphatase [BAP] and tartrate-resistant acid phosphatase [TRAP]) and the vascular calcification inhibitors, Matrix Gla Protein (MGP) and fetuin A were determined. HMD was measured at the lumbar spine, total hip, femoral neck and forearm. Arterial stiffness was assessed by contour analysis of digital volume pulse (SIovp)-Univariate and multiple linear regression analyses were undertaken. -- Results: FGF-23 was found to be elevated in CKD 3 compared to CKD 1, 2 although no significant differences in serum phosphate were observed. Serum phosphate (p

Fibroblast growth factor 23 (FGF-23), is recently discovered phosphaturic substance. It releases from bone osteocytes and plays a key role in the physiological regulation of phosphate metabolism. Excessive action of FGF23 results in several hypophosphatemic diseases characterized by impaired renal tubular phosphate reabsorption. In contrast, deficient action of FGF23 causes familial hyperphosphatemic tumoral calcinosis with enhanced renal tubular phosphate reabsorption. We carried out this study to gain knowledge about the current status of FGF-23 levels in our population and its relationship with serum phosphate; TmP/GFR and dietary phosphate; which has implications for the diagnosis and treatment of phosphate-wasting disorders and may guide us in planning further studies to see its role and implications on vitamin D metabolism.

αKlotho and fibroblast growth factor-23 (FGF23) were discovered independently about 20 years ago. Since their initial description, a series of exciting discoveries have revealed the important role of endocrine and paracrine FGF23 and αKlotho signaling not only for the physiological regulation of mineral and bone homeostasis, but also for the pathophysiology of diseases such as chronic kidney disease, left ventricular hypertrophy, myocardial infarction, hypertension, and disorders characterized by impaired bone mineralization. The 11 articles compiled in this Research Topic consist of three Original Research articles and 8 Reviews or Mini Reviews, and are an excellent source of information about the state of the art in the FGF23/αKlotho field, covering almost all aspects of FGF23/αKlotho biology.

Fibroblast growth factors (FGFs) have been recognized primarily as autocrine/paracrine factors that regulate embryonic development and organogenesis. However, recent studies have revealed that some FGFs function as endocrine factors and regulate various metabolic processes in adulthood. Such FGFs, collectively called endocrine FGFs, are comprised of three members (FGF15/19, FGF21, and FGF23: FGF15 is the mouse ortholog of human FGF19). These endocrine FGFs share a common structural feature that enables the endocrine mode of action at the expense of the affinity to FGF receptors. To restore the affinity to FGF receptors in their target organs, the endocrine FGFs have designated the Klotho family of transmembrane proteins as obligate co-receptors. By expressing Klothos in a tissue-specific manner, this unique co-receptor system also enables the endocrine FGFs to specify their target organs among many tissues that express FGF receptors.

This thesis focused on the question whether it is beneficial to modify FGF23 levels, in order to improve patient outcome. In chapter 1 an introduction to the thesis is given. The chapter provides a broader perspective on the possible clinical usefulness of FGF23 in the near future. Several aspects concerning the clinical use of FGF23 measurement are discussed. Up to date there are no prospective intervention studies in humans aiming to reduce FGF23 concentrations and testing whether cardiovascular morbidity and mortality is improved by this approach.Ahead of such a trial we studied in chapter 2.1 the natural course of FGF23 levels on clinical outcome. We explored to what extend the spontaneous change of FGF23 levels over time outperforms a single measurements as indicator of future cardiovascular events and mortality. However, we did not found that multiple FGF23 measurements are more strongly associated with outcome than a single measurement. . This study did confirm earlier studies by demonstrating that a single FGF23 measurement is an important risk factor for cardiovascular disease, as FGF23 was significantly associated with a composite of cardiovascular events, all-cause mortality and the initiation of renal replacement. In chapter 2.2 a meta-analysis of FGF23 and its associations with different outcomes and in the different populations is described In chapter 3 we investigated if the association of FGF23 with risk might be partially the result of this FGF23 resistance instead of FGF23 perse. In this study of a cohort of patients with CKD stage 3-4 the association of FGF23 with outcome was not influenced by the fractional excretion of phosphate, suggesting that resistance to FGF23 does not contribute to the adverse outcome related to elevated FGF23 levels. In chpater 4 we investigated an intervention assumed to lower FGF23 and its effect on pulse wave velocity (PWV).