title: Soluble TWEAK and PTX3 in nondialysis CKD patients: impact on endothelial dysfunction and cardiovascular outcomes.
abstract: OBJECTIVE
  Chronic kidney disease (CKD) conveys high mortality rates. Soluble TNF-like weak inducer of apoptosis (sTWEAK) and long pentraxin 3 (PTX3) are predictors of mortality in dialysis patients and determinants of endothelial dysfunction. Now, we hypothesize that both sTWEAK and PTX3 act as biomarkers of cardiovascular outcomes in nondialysis CKD patients.
  
  
  METHODS
  Cross-sectional analysis in which flow-mediated dilation (FMD) and intima-media thickness (IMT) were assessed in 257 nondialysis stage 1 to 5 CKD patients (mean age, 52 ± 12 years; 130 men), together with biochemical measurements and sTWEAK and PTX3 assessments. Patients were followed for cardiovascular outcomes.
  
  
  RESULTS
  PTX3 and IMT increased, whereas FMD and sTWEAK decreased across CKD stages (P<0.001 for all). Both PTX3 and sTWEAK appeared as strong determinants of FMD in multivariate analysis. The univariate associations of sTWEAK and PTX3 with IMT were dependent on estimated GFR. After a median of 39 months (range, 2 to 43 months), 22 fatal and 57 nonfatal cardiovascular events occurred. In a Cox model excluding PTX3, decreasing sTWEAK concentration was associated with increased risk of cardiovascular events independently of basic confounders (age, gender, estimated GFR, C reactive protein, diabetes, and cardiovascular comorbidity) and FMD. In a model excluding sTWEAK, circulating levels of PTX3 were directly associated with cardiovascular outcomes independently of basic confounders, but this association was lost after adjustment for FMD.
  
  
  CONCLUSIONS
  Both PTX3 and sTWEAK levels associated with the endothelial dysfunction observed with progressive kidney failure. Additionally, both biomarkers impacted the predictability of cardiovascular outcomes.
authors.affiliation: Department of Nephrology, Gu¨lhane School of Medicine, Ankara, Turkey.
authors.forename: Mahmut Ilker
authors.initials: MI
authors.lastname: Yilmaz
authors.forename: Alper
authors.initials: A
authors.lastname: Sonmez
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.forename: Mutlu
authors.initials: M
authors.lastname: Saglam
authors.forename: Selim
authors.initials: S
authors.lastname: Kilic
authors.forename: Tayfun
authors.initials: T
authors.lastname: Eyileten
authors.forename: Kayser
authors.initials: K
authors.lastname: Caglar
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Oguz
authors.forename: Abdulgaffar
authors.initials: A
authors.lastname: Vural
authors.forename: Mustafa
authors.initials: M
authors.lastname: Çakar
authors.forename: Jesus
authors.initials: J
authors.lastname: Egido
authors.forename: Battal
authors.initials: B
authors.lastname: Altun
authors.forename: Mujdat
authors.initials: M
authors.lastname: Yenicesu
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Blanco-Colio
authors.forename: Juan Jesús
authors.initials: JJ
authors.lastname: Carrero
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis* / Q000502:physiology; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D000074049:Cytokine TWEAK; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000683:Serum Amyloid P-Component / Q000032:analysis* / Q000502:physiology; D048069:Tumor Necrosis Factors / Q000097:blood* / Q000502:physiology; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D014664:Vasodilation; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D000074049:Cytokine TWEAK; D000683:Serum Amyloid P-Component; D048069:Tumor Necrosis Factors; D000099153:Pentraxins; C109743:TNFSF12 protein, human