2008 JASN IMPACT FACTOR 7.505	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text (Rapid PDF) All Versions of this Article: ASN.2005020155v1 17/1/199    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schwenger, V. Articles by Zeier, M. Search for Related Content PubMed PubMed Citation Articles by Schwenger, V. Articles by Zeier, M.

Received February 10, 2005
Accepted on October 18, 2005

BASIC SCIENCE: Basic Dialysis

Damage to the Peritoneal Membrane by Glucose Degradation Products Is Mediated by the Receptor for Advanced Glycation End-Products

Vedat Schwenger ^*1, Christian Morath ^*, Alexander Salava ^*, Kerstin Amann , Yuri Seregin ^*, Reinhold Deppisch , Eberhard Ritz ^*, Angelika Bierhaus ^*, Peter P. Nawroth ^*, and Martin Zeier ^*

*Department of Medicine, Divisions of Nephrology and Endocrinology, University of Heidelberg, Heidelberg, Germany; Department of Pathology, University of Erlangen-Nurnberg, Erlangen, Germany; and Gambro Corporate Research, Hechingen, Germany

¹ To whom correspondence should be addressed. E-mail: vedat.schwenger{at}med.uni-heidelberg.de.

	Abstract

Peritoneal dialysis is limited by morphologic changes of the peritoneal membrane. Use of peritoneal dialysis fluids (PDF) that contain glucose degradation products (GDP) generates advanced glycation end-products (AGE) within the peritoneal cavity. It is unknown whether peritoneal damage is causally related to AGE-receptor for AGE (RAGE) interaction. The effects of PDF were compared with different amounts of GDP on morphologic changes of the peritoneal membrane in 48 wild-type (WT) and 48 RAGE-deficient mice. PDF (1 ml) were instilled twice daily over a period of 12 wk. Groups with eight animals each received no manipulation (sham); sham instillation (sham i.p.); or filter-sterilized, glucose-free, conventional low GDP- or high GDP PDF. In vitro (generation of AGE fluorescence in PDF) and in vivo (immunohistochemistry for carboxymethyllysine), a GDP-dependent increase of AGE formation occurred. Inflammation and neoangiogenesis were augmented in WT mice that were treated with high GDP accompanied by upregulation of CD3+ T cells, increased NF-B binding activity, increased lectin, and vascular endothelial growth factor expression. Furthermore, pronounced submesothelial fibrosis was found with increased expression of TGF-1. Exposure to low GDP resulted in only mild inflammation and neoangiogenesis (compared with sham i.p.) and no fibrosis in WT mice. The findings in WT contrasted with those in RAGE-deficient mice, which showed no increased inflammation (CD3+ T cells and NF-B binding activity), neoangiogenesis (by lectin and vascular endothelial growth factor expression), or fibrosis (expression of TGF-1) after long-term exposure to GDP-containing PDF. Peritoneal damage by GDP in PDF is dependent at least in part on AGE-RAGE interaction.

This article has been cited by other articles:

				M. N. Schilte, J. W.A.M Celie, P. M. t. Wee, R. H.J. Beelen, and J. van den Born FACTORS CONTRIBUTING TO PERITONEAL TISSUE REMODELING IN PERITONEAL DIALYSIS Perit. Dial. Int., November 1, 2009; 29(6): 605 - 617. [Abstract] [Full Text] [PDF]

				A. Nakao, K. Nakao, Y. Takatori, S. Kojo, J. Inoue, S. Akagi, H. Sugiyama, J. Wada, and H. Makino Effects of icodextrin peritoneal dialysis solution on the peritoneal membrane in the STZ-induced diabetic rat model with partial nephrectomy Nephrol. Dial. Transplant., September 16, 2009; (2009) gfp479v1. [Abstract] [Full Text] [PDF]

				P. M. Humpert, I. K. Lukic, S. R. Thorpe, S. Hofer, E. M. Awad, M. Andrassy, E. K. Deemer, M. Kasper, E. Schleicher, M. Schwaninger, et al. AGE-modified albumin containing infusion solutions boosts septicaemia and inflammation in experimental peritonitis J. Leukoc. Biol., September 1, 2009; 86(3): 589 - 597. [Abstract] [Full Text] [PDF]

				I. Hirahara, Y. Ishibashi, S. Kaname, E. Kusano, and T. Fujita Methylglyoxal induces peritoneal thickening by mesenchymal-like mesothelial cells in rats Nephrol. Dial. Transplant., February 1, 2009; 24(2): 437 - 447. [Abstract] [Full Text] [PDF]

				J. Gozdzikiewicz, J. Borawski, and M. Mysliwiec Pleiotropic Effects of Heparin and Heparinoids in Peritoneal Dialysis Clinical and Applied Thrombosis/Hemostasis, February 1, 2009; 15(1): 92 - 97. [Abstract] [PDF]

				S. Latcha, S. Hong, N. Gibbons, N. Kohn, and J. Mattana Relationship between dialysate oxidized protein and peritoneal membrane transport properties in patients on peritoneal dialysis Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3295 - 3301. [Abstract] [Full Text] [PDF]

				L. P. Kihm, D. Wibisono, S. Muller-Krebs, F. Pfisterer, C. Morath, M. L. Gross, M. Morcos, Y. Seregin, A. Bierhaus, P. P. Nawroth, et al. RAGE expression in the human peritoneal membrane Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3302 - 3306. [Abstract] [Full Text] [PDF]

				H. Guo, J. C.K. Leung, M. F. Lam, L. Y.Y. Chan, A. W.L. Tsang, H. Y. Lan, and K. N. Lai Smad7 Transgene Attenuates Peritoneal Fibrosis in Uremic Rats Treated with Peritoneal Dialysis J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2689 - 2703. [Abstract] [Full Text] [PDF]

				K. N. Lai, S. C.W. Tang, and J. C.K. Leung MEDIATORS OF INFLAMMATION AND FIBROSIS Perit. Dial. Int., June 1, 2007; 27(Supplement_2): S65 - S71. [Abstract] [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673