title: Fibroblast growth factor-23 helps explain the biphasic cardiovascular effects of vitamin D in chronic kidney disease.
abstract: Hypovitaminosis D is highly prevalent in chronic kidney disease (CKD). Recently, vitamin D has sparked widespread interest because of its potential favorable benefits on cardiovascular disease (CVD). Evidence from clinical studies and animal models supports the existence of biphasic cardiovascular effects of vitamin D, in which lower doses suppress CVD and higher doses stimulate CVD. However, the mechanism for the different effects remains unclear. Fibroblast growth factor-23 (FGF-23) is a recently identified member of the FGF family, and thought to be actively involved in renal phosphate and vitamin D homeostasis. More specifically, Vitamin D stimulates FGF-23 secretion and is inhibited by increased FGF-23. Given this background, we hypothesize that FGF-23 may provide a unique tool to explain the biphasic cardiovascular effects of vitamin D in CKD. The data presented in this review support the hypothesis that FGF-23 may be linked with the high cardiovascular risk in CKD through accelerating the onset of vascular calcification, secondary hyperparathyroidism, left ventricular hypertrophy and endothelial dysfunction. Therefore, modulation of FGF-23 may become a potential therapeutic target to lowing cardiovascular risk in CKD. Several clinical interventions, including decreased phosphate intake, phosphate binders, cinacalcet plus concurrent low-dose vitamin D, C-terminal tail of FGF-23 and renal transplantation, have been employed to manipulate FGF-23.
authors.affiliation: Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, No. 218 Ji-Xi Road, Hefei 230022, PR China. hupeng28@yahoo.com.cn
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xuan
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yuan Han
authors.initials: YH
authors.lastname: Qin
mesh_terms: D000818:Animals; D057966:Calcimimetic Agents / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology; D002614:Chelating Agents / Q000627:therapeutic use; D000069449:Cinacalcet; D004032:Diet; D004730:Endothelium, Vascular / Q000503:physiopathology; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000503:physiopathology*; D016030:Kidney Transplantation; D008297:Male; D009281:Naphthalenes / Q000627:therapeutic use; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000008:administration & dosage; D011073:Polyamines / Q000627:therapeutic use; D051436:Renal Insufficiency, Chronic / Q000150:complications; D000069603:Sevelamer; D061205:Vascular Calcification / Q000209:etiology; D014807:Vitamin D / Q000009:adverse effects / Q000627:therapeutic use*; D014808:Vitamin D Deficiency / Q000209:etiology
chemical_list: D057966:Calcimimetic Agents; D002614:Chelating Agents; C000717427:FGF23 protein, human; D009281:Naphthalenes; D010281:Parathyroid Hormone; D010710:Phosphates; D011073:Polyamines; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000069603:Sevelamer; D000069449:Cinacalcet