title: The metabolic hormone FGF21 is associated with endothelial dysfunction in hemodialysis patients.
abstract: OBJECTIVE
  Finding new, reliable biomarkers of cardiovascular risk in hemodialysis (HD) patients is of utmost importance. Fibroblast growth factor 21 (FGF21) has been recently associated with atherosclerosis in the general population. The relationship between markedly elevated FGF21 levels in HD patients and endothelial dysfunction is unknown. The aim of the study was to assess the determinants of FGF21, the correlation between FGF21 and tumor necrosis factor TNF-like weak inducer of apoptosis (sTWEAK) and the correlation between FGF21 and endothelial dysfunction in HD patients.
  
  
  METHODS
  A cross-sectional observational study was conducted in 70 HD patients (mean age 59.9 ± 12.5 years, 14.3% diabetes mellitus, 57.1% male) from Nefromed Dialysis Center Cluj. We registered clinical and biological data, and serum FGF21 levels were measured by ELISA. Endothelial function was evaluated by brachial flow-mediated dilation (FMD). An analysis based on stratification of FGF21 values into quartiles was performed.
  
  
  RESULTS
  FGF21 levels were directly correlated with sTWEAK, tricipital skinfold thickness (TST), systolic blood pressure (SBP), total cholesterol and triglycerides. In multivariate linear analysis, only sTWEAK and SBP remained significantly associated with FGF21. FGF21 values in the inferior quartile were directly correlated with HDL-cholesterol, while FGF21 values in the superior quartile were directly correlated with SBP, pulse pressure and sTWEAK. FMD was significantly higher in the inferior quartile as compared to the superior quartile.
  
  
  CONCLUSIONS
  High FGF21 values in our patients are correlated with atherosclerosis risk factors: hypercholesterolemia, hypertriglyceridemia, hypertension, increased TST and increased levels of sTWEAK. Endothelial dysfunction is associated with high FGF21 in HD patients.
authors.affiliation: Department of Nephrology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 3-5 Clinicilor Street, 400006, Cluj-Napoca, Romania. crinaclaudiarusu@yahoo.ro.
authors.forename: Crina Claudia
authors.identifier: http://orcid.org/0000-0001-7708-9320
authors.initials: CC
authors.lastname: Rusu
authors.affiliation: Nefromed Dialysis Center, 40 Ana Aslan Street, Cluj-Napoca, Romania.
authors.forename: Simona
authors.initials: S
authors.lastname: Racasan
authors.affiliation: Department of Nephrology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 3-5 Clinicilor Street, 400006, Cluj-Napoca, Romania.
authors.forename: Ina Maria
authors.initials: IM
authors.lastname: Kacso
authors.affiliation: Department of Nephrology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 3-5 Clinicilor Street, 400006, Cluj-Napoca, Romania.
authors.forename: Diana
authors.initials: D
authors.lastname: Moldovan
authors.affiliation: Department of Nephrology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 3-5 Clinicilor Street, 400006, Cluj-Napoca, Romania.
authors.forename: Alina
authors.initials: A
authors.lastname: Potra
authors.affiliation: Department of Nephrology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 3-5 Clinicilor Street, 400006, Cluj-Napoca, Romania.
authors.forename: Dacian
authors.initials: D
authors.lastname: Tirinescu
authors.affiliation: Nefromed Dialysis Center, 40 Ana Aslan Street, Cluj-Napoca, Romania.
authors.forename: Cristian
authors.initials: C
authors.lastname: Budurea
authors.affiliation: Nefromed Dialysis Center, 40 Ana Aslan Street, Cluj-Napoca, Romania.
authors.forename: Remus
authors.initials: R
authors.lastname: Orasan
authors.affiliation: Nefromed Dialysis Center, 40 Ana Aslan Street, Cluj-Napoca, Romania.
authors.forename: Ioan Mihai
authors.initials: IM
authors.lastname: Patiu
authors.affiliation: Department of Informatics and Biostatistics, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 6 Pasteur Street, 400349, Cluj-Napoca, Romania.
authors.forename: Cosmina Ioana
authors.initials: CI
authors.lastname: Bondor
authors.affiliation: Department of Nephrology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 3-5 Clinicilor Street, 400006, Cluj-Napoca, Romania.
authors.forename: Dan
authors.initials: D
authors.lastname: Vladutiu
authors.affiliation: Department of Nephrology, University of Medicine and Pharmacy "Iuliu Hatieganu" Cluj, 3-5 Clinicilor Street, 400006, Cluj-Napoca, Romania.
authors.forename: Mirela Gherman
authors.initials: MG
authors.lastname: Caprioara
mesh_terms: D000368:Aged; D001794:Blood Pressure; D008076:Cholesterol, HDL / Q000097:blood; D003430:Cross-Sectional Studies; D000074049:Cytokine TWEAK; D004727:Endothelium / Q000503:physiopathology*; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000097:blood* / Q000628:therapy; D012885:Skinfold Thickness; D013599:Systole; D014280:Triglycerides / Q000097:blood; D048069:Tumor Necrosis Factors / Q000097:blood*; D014664:Vasodilation
chemical_list: D008076:Cholesterol, HDL; D000074049:Cytokine TWEAK; C109743:TNFSF12 protein, human; D014280:Triglycerides; D048069:Tumor Necrosis Factors; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors
keywords: Atherosclerosis risk; Endothelial dysfunction; FGF21; Hemodialysis; sTWEAK