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- Title
AGE Mediated Peritoneal Damage in Peritoneal Dialysis Is Related to RAGE -- Studies in a Model of RAGE Knock-Out Mice.
- Authors
Schwenger, V.; Morath, C.; Salava, A.; Deppisch, R.; Ritz, E.; Amann, K.; Bierhaus, A.; Nawroth, P.; Zeier, M.
- Abstract
Objective: Long-term peritoneal dialysis (PD) is associated with structural and functional changes of the peritoneal membrane. Recently in mesothelial cells the interaction of AGEs and RAGE has been reported. PD-fluid is a source of AGE due to nonenzymatic glycosylation of proteins. To further clarify the interaction of AGE and RAGE during PD fluid exposure, we examined the long-term effects of PD fluids in wild type (WT) and RAGE knock-out (k.o.) mice, using PD-fluid with conventional high and low GDP (glucose degradation products = carbonyl compunds) concentrations. Methods: Different (4% glucose either with conventional high or low glucose degradation products -- GDP) PD fluids (6 ml/100mg body weight) were administered to 18 WT and 18 and k.o. mice twice daily by microinjection for a period of 12 weeks, and compared to sham injected animals. Biopsies from peritoneal membrane assessed markers of inflammation (CD4+ cells), angiogenesis (% vessels/area) and fibrosis (histological score). Results: WT treated mice with regular GDP fluid had increased markers of inflammation, angiogenesis and fibrosis compared to sham treated WT mice (table 1 + 2). Interestingly WT mice treated with low GDP fluid had a higher score of angiogenesis, however less inflammation and fibrosis. In contrast RAGE k.o. mice had an increased score of angiogenesis and inflammation at baseline and no further increase after long-term PD fluid (either conventional or low GDP). Conclusions: AGE mediated induction of peritoneal toxicity is dependent on RAGE. Peritoneal toxicity is less in WT mice treated with low GDP fluids compared to WT mice treated with regular GDP content in the PD fluid.
- Subjects
PERITONEAL dialysis; MICE; INFLAMMATION; FLUID mechanics; NEOVASCULARIZATION; HYDROSTATICS; MONOSACCHARIDES; GLYCOSYLATION
- Publication
Kidney & Blood Pressure Research, 2004, Vol 27, Issue 5/6, p295
- ISSN
1420-4096
- Publication type
Article