title: High circulating levels of large splice variants of tenascin-C is associated with mortality and cardiovascular disease in chronic kidney disease patients.
abstract: OBJECTIVE
  Tenascin-C (TN-C) is an adhesion-modulating extracellular matrix glycoprotein which is overexpressed in various organs under disease conditions (infection and inflammation). In patients with heart disease, plasma TN-C levels have been shown to be predictive of cardiac remodeling. Chronic kidney disease (CKD) is associated with a state of chronic inflammation and high cardiovascular morbidity and mortality.
  
  
  METHODS
  In a prospective observational study, we examined the relationship between plasma concentration of large splice variants of TN-C (cTN-C) and cardiovascular outcomes, we studied a cohort of 94 prevalent CKD patients (mean±SD age: 68±13; 31% at CKD stages 2-3, 31% at stages 4-5, 38% at stage 5D).
  
  
  RESULTS
  Plasma cTN-C levels were elevated in this population and tended to rise as CKD progressed, with the increase becoming statistically significant at CKD stage 4-5 and 5D. Multivariate linear regression analysis indicated that CKD stage (p=0.04), IL-6 (p=0.02) and albumin (p=0.02) were independently associated with plasma cTN-C levels. During follow-up (mean duration: 969±405 days), 32 patients died (19 from CV events, 7 from infectious diseases and 6 from other causes). In a crude analysis, higher plasma cTN-C levels predicted overall and CV mortality (p=0.007 and p=0.003, respectively) and were associated with higher occurrence of CV events. Cox analyses confirmed that elevated plasma cTN-C levels were independently associated with cardiovascular events, cardiovascular and overall mortality.
  
  
  CONCLUSIONS
  Our findings suggest, for the first time, that plasma cTN-C levels are independently associated with cardiovascular outcomes in CKD patients. Further studies are needed in order to confirm the above observations and better understand TN-C's role in cardiovascular remodeling in CKD.
authors.affiliation: INSERM ERI-12 (EA 4292), Amiens, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Liabeuf
authors.forename: Daniela V
authors.initials: DV
authors.lastname: Barreto
authors.forename: Axel
authors.initials: A
authors.lastname: Kretschmer
authors.forename: Fellype C
authors.initials: FC
authors.lastname: Barreto
authors.forename: Cédric
authors.initials: C
authors.lastname: Renard
authors.forename: Michel
authors.initials: M
authors.lastname: Andrejak
authors.forename: Gabriel
authors.initials: G
authors.lastname: Choukroun
authors.forename: Ziad
authors.initials: Z
authors.lastname: Massy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001018:Aortic Diseases / Q000000981:diagnostic imaging; D002097:C-Reactive Protein / Q000378:metabolism; D002114:Calcinosis / Q000000981:diagnostic imaging; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality; D014644:Genetic Variation; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality*; D011446:Prospective Studies; D019063:Tenascin / Q000097:blood* / Q000235:genetics; D036542:Tomography, Spiral Computed; D020257:Ventricular Remodeling
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D019063:Tenascin; D002097:C-Reactive Protein