title: Glucose degradation products result in cardiovascular toxicity in a rat model of renal failure.
abstract: BACKGROUND
  It has been shown that glucose degradation products (GDP) generated during heat sterilization of peritoneal dialysis (PD) fluids impair the peritoneal membrane locally, then enter the systemic circulation and cause damage to the remnant kidney. Here we examined in subtotally nephrectomized (SNX) rats whether GDP also affect the cardiovascular system.
  
  
  METHODS
  Standard 5/6 nephrectomy was carried out in Sprague-Dawley rats; other rats were sham operated and left untreated for 3 weeks. Through an osmotic mini-pump, SNX+GDP group received GDP intravenously for 4 weeks; the SNX and the sham-operated groups remained without GDP. The experiment was terminated for all groups 7 weeks postoperatively. We analyzed cardiovascular damage by serum analyses and immunohistochemical investigation.
  
  
  RESULTS
  In SNX+GDP animals, expression of the advanced glycation end product (AGE) marker carboxymethyllysine and receptor of AGE (RAGE) were significantly higher in the myocardium and the aorta compared to the SNX rats. We also found significantly higher levels of apoptosis measured by caspase 3 staining in the cardiovascular system in the SNX+GDP group. Moreover, we observed a more pronounced expression of oxidative stress in the SNX+GDP rats compared to the SNX rats. In serum analyses, advanced oxidation protein products and reactive oxygen species were increased, as was immunohistochemical endothelial nitric oxide synthase.
  
  
  CONCLUSIONS
  In addition to local toxic effects, GDP cause systemic toxicity. Here we showed that, in SNX rats, administration of GDP increased cardiovascular damage. In particular, we found increased levels of AGE, RAGE, oxidative stress, and apoptosis. Whether these findings are of clinical relevance has to be further investigated.
authors.affiliation: Department of Nephrology, University of Heidelberg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Müller-Krebs
authors.forename: Lars P
authors.initials: LP
authors.lastname: Kihm
authors.forename: Benjamin
authors.initials: B
authors.lastname: Zeier
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Gross
authors.forename: Anders
authors.initials: A
authors.lastname: Wieslander
authors.forename: Ulrike
authors.initials: U
authors.lastname: Haug
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.forename: Vedat
authors.initials: V
authors.lastname: Schwenger
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000150:complications* / Q000378:metabolism*
chemical_list: D005947:Glucose