title: Advanced glycation end products and mortality in hemodialysis patients.
abstract: BACKGROUND
  Advanced glycation and oxidation end products (AGEs) cause oxidative stress and trigger cytokine driven inflammatory reactions in vitro. The net effects on markers of inflammation and acute phase proteins in vivo as well as their influence on survival in hemodialysis patients are unknown.
  
  
  METHODS
  We conducted a cross-sectional study in 312 stable hemodialysis patients and analyzed the interrelationships of AGEs and C-reactive protein (CRP) and their predictive effect on all-cause as well as cardiovascular mortality. Mortality was monitored prospectively over a period of 32 months. AGEs were determined by measuring total serum fluorescent AGEs (AGE-fl) and Nepsilon-(carboxymethyl)-lysine (CML).
  
  
  RESULTS
  The levels of AGE-fl, CML and CRP were 3.2-, 3.8- and 10-fold higher as compared to healthy controls. AGE-fl and CML levels correlated significantly with each other but not with CRP or serum albumin. Patients with high (above median values) AGE-fl or CML levels (109 x 103 AU and 1.4 microg/mL, respectively) had a significant better survival than those with low (below median values) AGE-fl or CML levels. Patients with high CRP levels (above 7.7 mg/L = median value) had a better survival than those with low CRP (below median value) when AGE-fl or CML levels were high in parallel.
  
  
  CONCLUSIONS
  In contrast to in vitro data and to current hypotheses, the presence of high serum AGEs, as measured by AGE-fl and CML, were not linked to increased mortality. Statistically, high serum AGEs partly overcame the negative impact of the acute phase response on mortality in hemodialysis patients. Whether the benefit of high serum AGEs is an epiphenomenon or reflects a better nutritional support needs further studies.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Würzburg Biocenter, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany.
authors.forename: Susanne B
authors.initials: SB
authors.lastname: Schwedler
authors.forename: Thomas
authors.initials: T
authors.lastname: Metzger
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schinzel
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000494:pharmacology; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000401:mortality*; D012709:Serum Albumin / Q000032:analysis; D015996:Survival Rate
chemical_list: D017127:Glycation End Products, Advanced; D012709:Serum Albumin; C048496:N(6)-carboxymethyllysine; D002097:C-Reactive Protein; D008239:Lysine; D001241:Aspirin