<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.
This work demonstrates that a comprehensive strategy of proteomic identification should be a useful tool for understanding of diabetic encephalopathy mechanism. And the differential proteins such as MLCK may be give clues about the pathogenesis of diabetic encephalopathy.
Introduction Osteoporosis is one of the important bone abnormalities in chronic kidney disease-mineral and bone disorder (CKD-MBD) and still lacks a sensitive biomarker to diagnose. Fibroblast growth factor 21 (FGF21) can stimulate bone loss in patients with diabetes and increase in CKD patients. In this study, we investigated whether FGF21 could serve as a biomarker to predict osteoporosis in a haemodialysis cohort. Methods We recorded demographic information, biochemical data, and serum FGF21 and FGF23 levels and measured the CT attenuation values of 339 haemodialysis patients from two large medical centres. We assessed the correlation of CT attenuation values with serum FGF21 and FGF23 levels and tested whether they were independent factors for osteoporosis. ROC curves were constructed to compare the prognostic value of FGF21 and FGF23 for osteoporosis. Results Based on the CT attenuation value, serum FGF21 levels were higher in our osteoporosis group (median 640.86 pg/ml vs. 245.46 pg/ml, P ˂ 0.01). Meanwhile, FGF21 (r = -0.136, P < 0.05) and FGF23 (r = -0.151, P < 0.05) were both negatively associated with osteoporosis. Moreover, FGF21 (β = -0.067, P < 0.05) was an independent factor for osteoporosis. Furthermore, FGF21 combined with age yielded a marked specificity (90.5 %) and sensitivity (61.8 %) in predicting osteoporosis of haemodialysis patients with less residual renal function. Conclusions FGF21 has a positive relationship with the incidence of osteoporosis in patients on haemodialysis. FGF21 combined with age is a good predictive biomarker for osteoporosis in patients on haemodialysis, especially those with less residual renal function.
Background and Aims Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) has been recognized as a common complication and arises early in the course of CKD. Osteoporosis can be one form of renal osteodystrophy, one component of the bone abnormalities of CKD-MBD. Fibroblast growth factor 21 (FGF21) is increased progressively with a decline of renal function and higher FGF21 levels predict high all-cause mortality in hemodialysis patients. In recent studies, FGF21 has been approved to exert an inverse effect on bone mineral density. Hence, our study was performed to investigate the relationship and role of FGF21 in osteoporosis in our hemodialysis (HD) patients cohort. Method We screened HD patients in Nanjing Zhongda Hospital and The First People’s Hospital of Changzhou according to a strict inclusion criteria and exclusion criteria. We recorded demographic information, blood data before dialysis and serum FGF21, FGF23 levels and measured the CT-attenuation values (in Hounsfield units (HU)) of trabecular bone in L1 on axial images to evaluate the severity of osteoporosis. We used univariate analyses to compare the differences between two groups. Meanwhile, bivariate correlation analyses were performed to assess the correlation of L1 attenuation with serum FGF21, FGF23 and other clinical parameters. Stepwise multivariate linear regression analyses were employed to evaluate variables independently associated with attenuation values. We constructed ROC curves to calculate the AUC and compared the prognostic value of every independently associated factor or united factor to osteoporosis. All analyses were two-tailed, and a P < 0.05 was considered to be statistically significant. SPSS Software, version 18.0 was used for all statistical analyses. Results 339 HD patients from two big HD centers in China that met our standards were screened. The mean age of HD patients was 56.79 ± 15.60 years. 339 HD patients were divided into two groups osteoporosis (n = 98) and non-osteoporosis (n = 241) on the basis of HU level (L1 attenuation ≤ 135 HU). Remarkably, serum FGF21 were higher in osteoporosis compared to non- osteoporosis in HD patients (median 640.86 pg/ml vs. 245.46 pg/ml, P < 0.01). We also divided HD patients into two groups according to tertiles of serum FGF21 levels. Moreover, attenuation levels were negative associated independently with serum FGF21 (r=-0.136, P<0.05). To evaluate the different values of independent associated or united factors in predicting osteoporosis, receiver operating characteristic (ROC) curves was constructed. The area under the curve (AUC) for FGF21 combined with age yielded a marked increment (AUC=0.836, P=0.000) with a good sensitivity (93.8%). Conclusion In conclusion, elevated FGF21 level has a positive relationship with the incidence of osteoporosis in HD patients. Simultaneously, FGF21 in combination with age can be a predictive parameter of osteoporosis in HD patients.
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