title: Advanced glycation end-product peptides are associated with impaired renal function, but not with biochemical markers of endothelial dysfunction and inflammation, in non-diabetic individuals.
abstract: BACKGROUND
  Patients with end-stage renal disease as well as mild renal impairment have an increased risk for the development of cardiovascular disease. It has been suggested that advanced glycation end-products (AGEs) are involved in atherogenesis, possibly through induction of endothelial dysfunction and low-grade inflammation.
  
  
  METHODS
  In a cross-sectional, single-centre study, we investigated four groups of 20 non-diabetic subjects with a creatinine clearance ranging from normal (> 90 ml/min/1.73 m2) to < 31 ml/min/1.73 m2. We measured AGE-peptides, markers of endothelial dysfunction (von Willebrand factor, soluble E-selectin, plasminogen activator inhibitor-1, tissue-type plasminogen activator, soluble vascular cell adhesion molecule-1) and markers of inflammatory activity (soluble intercellular adhesion molecule-1, C-reactive protein, secretory phospholipase A2). We constructed composite endothelial dysfunction and inflammatory activity Z-scores using these markers.
  
  
  RESULTS
  AGE-peptides were independently related to creatinine clearance (standardized beta -0.55, 95% confidence interval (CI) -0.77 to -0.34, P < 0.001). AGE-peptides were not independently related to the individual markers of endothelial dysfunction and inflammation, nor to the composite endothelial dysfunction Z-score (standardized beta 0.08, 95% CI -0.14 to -0.30, P = 0.48) or the inflammatory activity Z-score (standardized beta -0.05, 95% CI -0.25 to -0.16, P = 0.66).
  
  
  CONCLUSIONS
  Plasma concentrations of AGE-peptides are associated with creatinine clearance but not with biochemical markers of endothelial dysfunction and inflammatory activity in non-diabetic patients over a wide range of renal function. This suggests that the atherogenic effects of AGE-peptides in individuals with renal functional impairment are not mediated by endothelial dysfunction or inflammatory activity as estimated by the markers used.
authors.affiliation: Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands. f.stam@vumc.nl
authors.forename: Frank
authors.initials: F
authors.lastname: Stam
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: Coen
authors.initials: C
authors.lastname: van Guldener
authors.forename: Piet M
authors.initials: PM
authors.lastname: ter Wee
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood; D007674:Kidney Diseases / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D017395:Plasminogen Activator Inhibitor 1; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D003404:Creatinine; D010959:Tissue Plasminogen Activator