Fibroblast Growth Factor 21 Predicts and Promotes Vascular Calcification in Haemodialysis Patients

Abstract

<b><i>Background:</i></b> Cardiovascular disease (CVD) is the leading cause of death in haemodialysis (HD) patients. Vascular calcification (VC) is dramatically accelerated and is strongly associated with CVD events and mortality in HD patients. VC coexists with osteoporosis in many studies. Fibroblast growth factor 21 (FGF21) which is known as an adipocytokine is a new hypoglycemic strategy and is inversely related to bone mineral density. <b><i>Methods:</i></b> To evaluate the contribution of FGF21 to VC in HD patients, we detected circulating FGF21 levels and measured the whole thoracic aorta calcification scores (TACS) and calcification scores of the 3 segments of thoracic aorta, including ascending thoracic aorta (ATACS), aortic arch (AoACS), and descending thoracic aorta (DTACS) of our HD patients in this cross-sectional study. In addition, we pre-incubated human aortic endothelial cells (HAECs) with FGF21 in the presence or absence of parathyroid hormone (PTH) in vitro. <b><i>Results:</i></b> The median serum FGF21 level in HD patients was 11-fold higher than that in healthy controls. Ln(FGF21) was positively correlated with Ln(TACS+1), Ln(ATACS+1), Ln(AoACS+1), and Ln(DTACS+1), respectively, in HD patients. Serum FGF21 was independently associated with TACS and ATACS, AoACS, and DTACS. FGF21 which was combined with age, calcium, and intact PTH demonstrated a high area under the curve of 0.84 with optimal sensitivity (84%) and specificity (71%) for the prediction of VC in HD patients. Our vitro results showed that FGF21 enhanced the calcification effect of PTH on HAECs by increasing calcium deposition and endothelial-to-mesenchymal transition. <b><i>Conclusions:</i></b> Circulating FGF21 was notably higher and was a potential predictor and promoter of VC in HD patients.

Fibroblast growth factor 21 predicts arteriovenous fistula functional patency loss and mortality in patients undergoing maintenance hemodialysis

“…[ 23 ] found that baseline FGF21 was an independent predictor of atherosclerotic cardiovascular disease via a survey of patients with atherosclerosis, and the risk of atherosclerotic cardiovascular disease was three times higher in patients with high FGF21 levels compared to patients with low FGF21 levels. Our preliminary results confirmed that serum FGF21 was a potential predictor and promoter of VC in patients undergoing MHD [ 12 ]. Because of the association of FGF21 with oxidative stress, inflammation, vascular calcification and atherosclerosis, it was reasonable to hypothesize that FGF21 was involved in the development of NIH and closely related to AVF functional patency loss.…”

“…Second, elevation of FGF21 is an adaptive response to pathological conditions, but it cannot counteract the damage caused by multiple noxious stimuli, such as uremia. Third, FGF21 may be a potential pathogenic agent that aggravates AVF failure and accelerates mortality because it is associated with calcification and CKD-mineral and bone disorders [ 12 , 35 ].…”

“…A commercial ELISA kit was used for FGF21 determination (Neobioscience, China). Assays were performed as previously described, following the manufacturer’s instructions [ 12 ]. The inter-assay and intra-assay coefficients of variation for FGF21 were less than 10%.…”

“…Elevated levels of FGF21 are associated with coronary artery disease [ 8 ], carotid atherosclerosis [ 9 ], and inflammatory responses (sepsis and ARDS) [ 10 , 11 ]. Our previous studies indicated that FGF21 cooperated with parathyroid hormone to promote the trans-differentiation of endothelial cells into osteoblasts, which promoted vascular calcification (VC) in patients undergoing MHD [ 12 ]. Due to the effects of FGF21 on oxidative stress, inflammation, calcification, and its pleiotropic metabolism, FGF21 may be an effective biomarker of AVF dysfunction.…”

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“…It has been clinically associated with VC in hemodialyzed patients. Serum FGF21 has been highly correlated with high calcium scores in three different thoracic aorta segments: ascending thoracic aorta, aortic arch, and descending aorta ( 54 ). Additionally, FGF21 has been correlated with the increasing grade of aortic stenosis ( 55 ).…”