P0667FIBROBLAST GROWTH FACTOR 21 PROMOTES AND PREDICTS VASCULAR CALCIFICATION IN HAEMODIALYSIS PATIENTS
Authors: Jiang Liqiong , Wang Bin , Liu Bicheng 
Published: June 2020

Background and Aims

Cardiovascular disease (CVD) is the leading cause of death in hemodialysis (HD) patients. Vascular calcification (VC) is dramatically accelerated and strongly associated with CVD events and mortality in HD patients. This study aimed to achieve 4 objectives using a population-based retrospective cohort of HD patients: (1)quantify the correlation between FGF21 and VC; (2)determine whether FGF21 is a novel risk factor for VC; (3)examine the predictive effect of FGF21 on VC; (4)explore the underlying mechanism of FGF21 in promoting VC, especially focused on the EndMT process, in cultured human aortic endothelial cells (HAECs).

Method

802 HD patients were screened, at last 388 HD patients were eligible in the study. Serum FGF21 levels were assessed by ELISA kits. Chest radiographies of HD patients taken by multislice computed tomography were used to measure TACS. HD patients were divided into two groups : low TACS group (&lt; median of TACS) and high TACS group (≧median of TACS). Univariate analyses were performed to compare the differences between two groups. Categorical data were compared using the Chi-square test. Stepwise multivariate linear regression analyses were employed to evaluate variables independently associated with TACS. The ROC curves were performed to calculate the AUC and compare the prognostic value of every independently associated factor or united factor to VC. Additionally HAECs was pretreated with FGF21 in the presence or absence of PTH. The formation of calcium deposits was analysed by Alizarin Red staining (ARS). PCR for the measurement of mRNA of CD31, RUNX2 and FSP1 to evaluate endothelial-to-mesenchymal transition (EndMT) of HAECs.

Results

Prevalence of VC was 70.1% in this study. Serum FGF21 levels of HD patients were 11-fold higher than controls (median 217 vs. 20 pg/ml). HD patients in the high TACS group had older age, higher FGF21, higher FGF23, longer dialysis vintage, higher incidence of hypertension and higher incidence of CVD (all P&lt;0.05) compared with those in the low TACS group. Ln (FGF21) was positively related with Ln (TACs+1) (r=0.295). ROC curves showed that the AUC of FGF21 for predicting TAC was 0.63 (P&lt;0.01), while FGF21 combined with other independent associated factors like age, calcium and PTH, the AUC markedly increased (AUC=0.84) with optimal sensitivity (82%) and specificity (71%). ARS showed that calcium deposition was observed in cultured HAECs stimulated by PTH alone and even aggravated by PTH+FGF21; however, no calcium deposition was observed in HAECs stimulated by FGF21 alone. Compared with the control, reduced expression of CD31(endothelial cell marker) mRNA in parallel with increased expression of RUNX2(osteoblast marker) mRNA and FSP1(mesenchymal cell marker) mRNA was observed in HAECs stimulated by PTH. However, FGF21 alone had no significant effect on the EndMT process. Notably, stimulation of PTH+FGF21 in HAECs aggravated the effect of PTH alone on EndMT.

Conclusion

This study is the first to show that serum FGF21 levels were significantly and independently correlated with VC in HD patients. Furthermore, FGF21 combined with PTH, calcium and age can significantly predict VC in HD patients. Additionally FGF21 aggravated the effect of PTH on calcium deposition and EndMT in HAECs. Taken together, our in vivo and in vitro results indicated that FGF21 was a novel predictor and promoter of VC in HD patients.