title: Low-molecular but not high-molecular advanced glycation end products (AGEs) are removed by high-flux dialysis.
abstract: BACKGROUND
  Patients with end-stage renal disease (ESRD) display very high levels of advanced glycation end products (AGEs). These compounds are suspected to play a pathophysiological role in diabetic nephropathy and late diabetic cardiovascular complications. We investigated to what extent AGE levels can be reduced by high-flux dialysis.
  
  
  METHODS
  Ten ESRD patients were treated three times each with DIAPES and HF60, two different synthetic, high-flux hemodialysis membranes. The kinetics of AGE removal was studied by fluorescence spectroscopy (excitation 370 nm/ emission 440 nm) and by ELISA of serum samples and the removal of beta2-m was studied by immunonephelometry of plasma samples. Samples were taken during dialysis sessions at t = 0, 30 and 180 min. In addition, molecular weight distribution of AGE products in serum of three patients was analyzed by gel filtration and fluorescence detection.
  
  
  RESULTS
  A significant difference could be found when AGE levels in serum of controls (n = 10) were compared with serum AGE levels of ESRD patients (p < 0.01/fluorescence; p < 0.0001/ ELISA). After 3 h of dialysis AGE-related fluorescence in serum decreased by 25.5 +/- 6.8% for HF60 (p < 0.0001) and 24.3 +/- 6.9% tor DIAPES (p < 0.0001). The corresponding decline measured by ELISA was 23.3 +/- 8.9% for HF60 (p < 0.0001) and 26.1 +/- 7.0% for DIAPES (p < 0.0001). Both methods showed no significant differences for both types of dialysis membranes. Gel filtration revealed that the decrease of fluorescence can be attributed to the removal of AGE peptides with a molecular mass < 12 kDa, only. In the high molecular range (> 12 kDa) no removal but hemoconcentration was observed independent of the dialyzer type used. The reduction of beta2-m during 3 hours of dialysis was 61.8 +/- 6.9% for HF60 (p < 0.0001) and 161.7 +/- 7.0% for DIAPES (p < 0.0001).
  
  
  CONCLUSIONS
  Both high-flux dialyzers were equally effective to remove low-molecular AGE products, while AGE-modified proteins of higher molecular weight were only marginally affected. On the basis of our data we suggest the study of molecular mass-dependent uremic toxicity of AGEs and the examination of the influence of other treatment modalities on the level of high-molecular AGEs.
authors.affiliation: Physiologische Chemie I, Biozentrum, Würzburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Gerdemann
authors.forename: H D
authors.initials: HD
authors.lastname: Lemke
authors.forename: A
authors.initials: A
authors.lastname: Nothdurft
authors.forename: A
authors.initials: A
authors.lastname: Heidland
authors.forename: G
authors.initials: G
authors.lastname: Münch
authors.forename: U
authors.initials: U
authors.lastname: Bahner
authors.forename: R
authors.initials: R
authors.lastname: Schinzel
mesh_terms: D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005453:Fluorescence; D017127:Glycation End Products, Advanced / Q000097:blood* / Q000737:chemistry; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood; D008875:Middle Aged; D008970:Molecular Weight; D006435:Renal Dialysis; D013997:Time Factors; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D001613:beta 2-Microglobulin