Role of fibroblast growth factor-23 in peripheral vascular calcification in non-diabetic and diabetic hemodialysis patients

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Fibroblast growth factor (FGF) 23 is a recently identified circulating factor that regulates phosphate (Pi) metabolism. Since the derangement of Pi control is an important risk factor for vascular calcification, we investigated the importance of plasma FGF-23 in the development of vascular calcification in the aorta and peripheral artery in hemodialysis patients with and without diabetes mellitus (DM). Male hemodialysis patients with DM (n=32) and without DM (n=56) were examined. Plasma samples were obtained before the start of dialysis sessions, and the FGF-23 levels were determined by enzyme-linked immunosorbent assay. Roentgenography of the aorta and hand artery was performed, and visible vascular calcification was evaluated by one examiner, who was blinded to the patient characteristics. In the 56 non-DM hemodialysis patients, vascular calcification was found in the hand artery in 5 patients (8.9%) and in the aorta in 23 patients (41.1%). These levels were significantly lower (p<0.05) than in the 32 DM patients, of whom, 19 (59.4%) and 21 (65.6%) had vascular calcification of the hand artery and aorta, respectively. Multiple regression analyses performed separately in the non-DM and DM patients showed that the plasma FGF-23 level, CaxPi product, and body weight are independent factors significantly associated with hand-artery calcification and that diastolic blood pressure is associated with aorta calcification in non-DM patients. In DM patients, the plasma FGF-23 level and hemodialysis duration emerged as independent factors associated with hand-artery calcification and diastolic blood pressure was associated with aorta calcification. The independent association of the plasma FGF-23 level with hand-artery calcification was retained in both non-DM and DM patients when adjusted for the CaxPi product. Our findings show that the plasma FGF-23 level is an independent factor negatively associated with peripheral vascular calcification in the hand artery, but not in the aorta, in both male non-DM and DM hemodialysis patients, even when adjusted for the CaxPi product. This study raises the possibility that the plasma FGF-23 level may provide a reliable marker for Moenckeberg's medial calcification in male hemodialysis patients, independent of its regulatory effect on Pi metabolism.