Effects of Low Glucose Degradation Products Peritoneal Dialysis Fluid on the Peritoneal Fibrosis and Vascularization in a Chronic Rat Model

Objective To review protein glycation and advanced glycation end-product formation with particular reference to its occurrence in the peritoneum following exposure to peritoneal dialysis fluid. Data sources Articles identified through searches on MEDLINE and BIDS and references cited therein. Study selection Studies on the interaction of amino groups with glucose, maltose and glucose polymers. Studies containing evidence of peritoneal advanced glycation end-product formation. Data extraction Studies evaluated as to whether they are in vivo, ex vivo or in vitro under non-physiological or physiological conditions. Results Protein glycation is slower with maltose and glucose polymers than with equimolar glucose. Advanced glycation end-product formation occurs with all three sugars, but to a greater extent after standard heat sterilization of dialysis fluid and to a lesser extent in heat sterilized fluids containing icodextrin rather than glucose. Glucose degradation products significantly contribute to protein-linked advanced glycation end-productlike fluorescence. Histology and immunohistochemistry demonstrate diabetiform changes and advanced glycation end-products in the peritoneal membrane following exposure to glucose-containing peritoneal dialysis fluids. Their presence is likely to be detrimental to peritoneal function and may contribute to loss of ultrafiltration. Conclusions Advanced glycation end-product formation is lower but still significant with heat sterilized peritoneal dialysis fluid containing icodextrin than with glucose. More research is needed to investigate the interaction of glucose degradation products and glucose polymers with proteins and the possible consequences of advanced glycation end-product formation on peritoneal function.

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Peritoneal Dialysis Solutions Low in Glucose Degradation Products—evidence for Clinical Benefits

Peritoneal Dialysis International ◽

10.1177/089686080802803s23 ◽

2008 ◽

Vol 28 (3_suppl) ◽

pp. 123-127

Author(s):

Tadashi Tomo

Keyword(s):

Peritoneal Dialysis ◽

Vascular Function ◽

Degradation Products ◽

Peritoneal Mesothelial Cells ◽

Advanced Glycosylation End Products ◽

Glucose Degradation Products ◽

Peritoneal Dialysis Fluid ◽

Clinical Benefits ◽

Human Peritoneal Mesothelial Cells ◽

Peritoneal Function

In Japan, two types of new peritoneal dialysis fluid (PDF) are ordinarily used: two-chambered PDF, and icodextrin PDF. Two-chambered PDF has several biocompatible characteristics, one being low glucose degradation products (GDPs). Of the several GDPs in PDF, 3,4-dideoxyglucosone-3-ene (3,4-DGE) is thought to be strongly associated with the cytotoxicity of standard PDF. Using a PDF low in GDPs may reduce exposure of the peritoneum to 3,4-DGE, helping to preserve peritoneal function in PD patients. Additionally, use of a PDF low in GDPs may reduce plasma levels of advanced glycosylation end-products in PD patients, a change that may help to preserve vascular function in PD patients. Peritoneal rest for 24 hours after exposure to a PDF with low GDPs improves the activity of human peritoneal mesothelial cells. As compared with the use of standard PDF, the use of low-GDP PDF in combination therapy (peritoneal dialysis plus hemodialysis) may more effectively preserve peritoneal function. The new PDF low in GDPs has bio-compatible characteristics relative to peritoneum and system that may help to preserve peritoneal function or reduce complications such as atherosclerosis or dialysis-related amyloidosis in dialysis patients.

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Glucose Degradation Products and the Peritoneal Mesothelium

Peritoneal Dialysis International ◽

10.1177/089686080002005s04 ◽

2000 ◽

Vol 20 (5_suppl) ◽

pp. 19-22 ◽

Cited By ~ 10

Author(s):

Achim Jörres ◽

Thorsten O. Bender ◽

Janusz Witowski

Keyword(s):

Peritoneal Dialysis ◽

Degradation Products ◽

Experimental Models ◽

Buffer System ◽

Peritoneal Fibrosis ◽

High Concentration ◽

Peritoneal Mesothelial Cells ◽

Cell Functions ◽

Glucose Degradation Products

Conventional heat-sterilized, glucose-based peritoneal dialysis (PD) fluids contain significant amounts of glucose degradation products (GDPs) such as aldehydes and dicarbonyl compounds (glyoxal, methylglyoxal). These GDPs have been shown to impair cell functions in various in vitro experimental models. In peritoneal mesothelial cells, GDPs dose-dependently inhibit cell proliferation and mediator synthesis. In addition, some GDPs potently promote generation of advanced glycation end-products (AGEs). Immunohistochemistry finds AGEs in the peritoneal membrane of chronic continuous ambulatory peritoneal dialysis (CAPD) patients, suggesting that peritoneal AGE accumulation may be involved in chronic peritoneal fibrosis. The formation of GDPs might be prevented by filter-sterilization of PD fluids. Another option is to separate the glucose and the buffer system in dual-chambered or multi-chambered containers. In these systems, the glucose is kept in a separate compartment at high concentration and very low pH—both conditions being known to minimize the degree of glucose decomposition during autoclaving. Initial experimental evidence suggests that these novel, multi-chambered fluids significantly improve in vitro biocompatibility; however, the clinical relevance of these results remains to be established in clinical trials.

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