title: Increased serum levels of GDF-15 associated with mortality and subclinical atherosclerosis in patients on maintenance hemodialysis.
abstract: OBJECTIVE
  Increased carotid intima-media thickness (CIMT) was shown to be an independent predictor of cardiovascular (CV) mortality in dialysis patients and the general population. Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor superfamily, is produced by cardiomyocytes and atherosclerotic lesions under stress conditions such as inflammation. We assessed associations between serum concentrations of GDF-15, mortality, and CIMT for subclinical atherosclerosis in hemodialysis (HD) patients.
  
  
  METHODS
  A total of 87 patients on maintenance hemodialysis and 45 sex- and age-matched healthy controls were included in this prospective study. Serum GDF-15 levels were measured by ELISA. CIMT was assessed by Doppler ultrasonography. The association between serum GDF-15 levels and mortality was assessed using Cox regression analysis with serum levels categorized into two groups according to the median value (328.18 pg/ml). Patients were followed for 2 years and cause-specific and all-cause mortality were determined.
  
  
  RESULTS
  The median level of serum GDF-15 was significantly higher in HD patients than controls [328 (198-522) vs. 176 (101-289) pg/ml, p < 0.01, respectively]. Serum GDF-15 levels were correlated to CIMT (r = 0.607, p < 0.001), C-reactive protein (CRP; r = 0.250, p = 0.010), HD duration (r = 0.376, p = 0.004), and serum albumin (r = - 0.156, p = 0.030). The multivariate analysis revealed that GDF-15 was found to be an independent variable of CIMT in HD patients. In the study, the serum GDF-15 level was an independent marker of all-cause of mortality when adjusted for age, CRP, and history of diabetes mellitus.
  
  
  CONCLUSIONS
  The relationship between serum GDF-15, mortality, and carotid artery thickening suggests that GDF-15 may be a novel marker of atherosclerosis, inflammation, and malnutrition in HD patients.
authors.affiliation: Department of Internal Medicine, Section of Nephrology, Turgut Ozal University School of Medicine, Alparslan Türkes Cad. No: 57, 06510, Emek/Ankara, Turkey, drhakkiyilmaz@yahoo.com.
authors.forename: H
authors.initials: H
authors.lastname: Yilmaz
authors.forename: H T
authors.initials: HT
authors.lastname: Çelik
authors.forename: O M
authors.initials: OM
authors.lastname: Gurel
authors.forename: M A
authors.initials: MA
authors.lastname: Bilgic
authors.forename: M
authors.initials: M
authors.lastname: Namuslu
authors.forename: H
authors.initials: H
authors.lastname: Bozkurt
authors.forename: A
authors.initials: A
authors.lastname: Ayyildiz
authors.forename: O
authors.initials: O
authors.lastname: Inan
authors.forename: N
authors.initials: N
authors.lastname: Bavbek
authors.forename: A
authors.initials: A
authors.lastname: Akcay
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D015415:Biomarkers / Q000097:blood*; D015897:Comorbidity; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000401:mortality*; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000401:mortality* / Q000628:therapy; D018570:Risk Assessment / Q000379:methods; D015996:Survival Rate; D014421:Turkey / Q000453:epidemiology; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15