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 specif-ically, 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 ac-celerating 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 interven-tions, 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. © Ivyspring International Publisher.