HDCN Abstract:  ASN Annual Meeting -- San Francisco  

Kaname S, Hirahara I, Ishibashi Y, et al.

High GDPs Solution Induces Peritoneal Fibrosis and Epithelial- Mesenchymal Transition in New Rat PD Model.

ASN Annual Meeting -- San Francisco
J Am Soc Nephrol (Nov) 18:690A 2007

Peritoneal fibrosis is a complication of peritoneal dialysis (PD) using glucose-based dialysates, which contain small amounts of glucose degradation products (GDPs). Here we developed new animal model for peritoneal fibrosis induced by methylglyoxal (MGO), a major GDP in conventional solutions. Using this model, we investigated pathogenic mechanism of peritoneal fibrosis, focusing on possible involvement of epithelial-mesenchymal transition (EMT).

Male SD rats were exposed to 100 mL/kg of dialysates (pH 5.0) without or with MGO (20 mM), or 10 mL/kg of 0.1% chlorhexidine gluconate (CHX) by intraperitoneal injection for 21 days. Parietal peritoneum was obtained to perform immunohistochemistry and analyze mRNA expression by RT-PCR. Matrix metalloproteinase (MMP) levels were evaluated by zymography, and concentrations of TGF- and VEGF determined by EIA. The MGO-treated rats showed peritoneal thickening and fibrosis, associated with increased membrane permeability by peritoneal equilibration test. The mRNA expression of type I collagen, TGF-, MMP-2, VEGF and RAGE was increased, and concentrations of MMP-2, TGF- and VEGF in peritoneal fluids were elevated. Moreover, mRNA expression of snail, marker of EMT, was significantly increased, and immunohistochemistry revealed that some of the cytokeratin-positive mesothelial cells showed - SMA statining. AGE was accumulated in the surface including mesothelial cells. In contrast, peritoneal mesothelial cells were almost absent and snail was not upregulated in CHX-treated rats, although marked peritoneal thickening was seen.

These results show that MGO-treated rat model mimics peritoneal changes during long-term PD rather than standard CHX model, and it was suggested that repeated treatment with GDPs may cause peritoneal fibrosis possibly by inducing EMT for mesothelial cells.

© Copyright 2007-2008, American Society of Nephrology. Reproduced with permission.
Until September of 2008, all ASN abstracts from the 2007 Annual Meeting are available at this link

Disclaimer: Abstracts often have errors, both typographical and otherwise. This posting is an electronic translation of submitted abstracts which has not been verified against the original submitted abstract nor with the authors for accuracy. As a result, there may be errors, especially with regard to drug doses, but not limited to these. Abstracts undergo only limited review, and data often are changed as a result of the peer review process, so their reliability is less than manuscripts published in peer-reviewed journals. In using these summaries, you are agreeing that you are aware of these limitations.

The materials are provided on an as-is basis without any warranty of any kind, either express or implied. In addition to errors, the information presented may be incomplete or outdated. The information contained is not intended nor recommended as a substitute for professional medical advice. You are advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each device to be used or drug to be administered to verify the dosage, the method and duration of administration, or contraindications. It is the responsibility of the treating physician or other health care professional, relying on independent experience and knowledge of the patient, to determine drug, disease, and the best treatment for the patient.

To the fullest extent permitted by law, HDCN, ASN and their affiliates and suppliers disclaim all warranties, express or implied, including, but not limited to, any warranty of merchantability, non- infringement or fitness for a particular purpose.

In no event shall HDCN, ASN, or their affiliates or suppliers be liable for any damages whatsoever (including, but not limited to, direct, indirect, incidental, consequential, punitive or exemplary damages, or any damages for loss of profits, use, data, goodwill or other intangibles) arising from or in any way relating to these terms, the materials, or any information, goods or services obtained from or referred to in the materials, whether based on warranty, contract, tort (including, but not limited to, negligence), or any other legal theory, and whether or not any or all of the limited entities is advised of the possibility of such damages.