title: Markers of vascular disease in plasma from patients with chronic kidney disease identified by proteomic analysis.
abstract: OBJECTIVE
  Chronic kidney disease (CKD) patients belong to the group of patients with a high prevalence of cardiovascular disease (CVD). Arterial calcification and aortic stiffness are currently used as surrogates for vascular alterations. However, still little is known about prediction and the patho-physiologic mechanisms leading to CVD.
  
  
  METHODS
  We applied capillary electrophoresis coupled mass spectrometry profiling to blood specimens collected from 34 CKD stage 5D patients suffering from vascular alterations to allow insights into the molecular pathology of the disease.
  
  
  RESULTS
  Statistical comparison of plasma profiles from mild and severe CVD cases according to either arterial calcification or aortic stiffness unveiled 13 novel biomarkers for vascular disease. Tandem mass spectrometry identified four of these as fragments of collagen alpha-1 type I and III and one as fragment of apolipoprotein CIII. Integrated in a distinct pattern the candidates were validated using the moderate CVD cases among the 34 CKD patients (N=11) and an additional independent blinded cohort of CKD stage 4-5 patients (N=21), who all had not been considered during biomarker discovery. The panel distinguished mild and severe CVD with sensitivity of 89% and specificity of 67% in this independent cohort.
  
  
  CONCLUSIONS
  This diagnostic phase I/II study supports the notion that vascular alterations are reflected by distinct changes in plasma profiles of CKD patients.
authors.affiliation: Mosaiques diagnostics GmbH, Hannover, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Schiffer
authors.forename: Sophie
authors.initials: S
authors.lastname: Liabeuf
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Lacroix
authors.forename: Mohamed
authors.initials: M
authors.lastname: Temmar
authors.forename: Cedric
authors.initials: C
authors.lastname: Renard
authors.forename: Bernard
authors.initials: B
authors.lastname: Monsarrat
authors.forename: Gabriel
authors.initials: G
authors.lastname: Choukroun
authors.forename: Horst-Dieter
authors.initials: HD
authors.lastname: Lemke
authors.forename: Raymond
authors.initials: R
authors.lastname: Vanholder
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
mesh_terms: D000368:Aged; D019075:Electrophoresis, Capillary; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D040901:Proteomics; D014652:Vascular Diseases / Q000097:blood* / Q000150:complications