Glucose degradation products result in cardiovascular toxicity in a rat model of renal failure.
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.
Müller-Krebs
Sandra
S
Department of Nephrology, University of Heidelberg, Germany.
Kihm
Lars P
LP
Zeier
Benjamin
B
Gross
Marie-Luise
ML
Wieslander
Anders
A
Haug
Ulrike
U
Zeier
Martin
M
Schwenger
Vedat
V
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*
D005947:Glucose