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

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.

scholarly journals Prolonged Exposure to Glucose Degradation Products Impairs Viability and Function of Human Peritoneal Mesothelial Cells

2001 ◽  
Vol 12 (11) ◽  
pp. 2434-2441 ◽  
Author(s):  
JANUSZ WITOWSKI ◽  
JUSTYNA WISNIEWSKA ◽  
KATARZYNA KORYBALSKA ◽  
THORSTEN O. BENDER ◽  
ANDRZEJ BREBOROWICZ ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Cell Viability ◽  
Degradation Products ◽  
Mesothelial Cells ◽  
Peritoneal Mesothelial Cells ◽  
Glucose Degradation Products ◽  
Human Peritoneal Mesothelial Cells ◽  
And Function ◽  
The Impact

Abstract. Bioincompatibility of peritoneal dialysis fluids (PDF) has been linked to the presence of glucose degradation products (GDP). Previous experiments have shown that short-term exposure to several GDP at concentrations found in commercially available PDF had no significant effect on human peritoneal mesothelial cells (HPMC). During continuous ambulatory peritoneal dialysis, however, cells are continually exposed to GDP for extended periods of time. Thus, the impact of GDP on HPMC during long-term exposure was assessed. HPMC were cultured for up to 36 d in the presence of 6 identified GDP (acetaldehyde, formaldehyde, furaldehyde, glyoxal, methylglyoxal, and 5-HMF) at doses that reflect their concentrations in conventional PDF. At regular time intervals, the ability of HPMC to secrete cytokines (interleukin-6 [IL-6]) and extracellular matrix molecules (fibronectin) was evaluated. In addition, cell viability, morphology, and proliferative potential were assessed. Exposure to GDP resulted in a significant reduction in mesothelial IL-6 and fibronectin release. Approximately 80% of this decrease occurred during the first 12 d of the exposure and was paralleled by a gradual loss of cell viability and development of morphologic alterations. After 36 d of exposure, the number of cells in GDP-treated cultures was reduced by nearly 60%. However, GDP-treated cells were able to resume normal proliferation when transferred to a normal GDP-free medium. HPMC viability and function may be impaired during long-term exposure to clinically relevant concentrations of GDP, which suggests a potential role of GDP in the pathogenesis of peritoneal membrane dysfunction during chronic peritoneal dialysis.

Glycation and Advanced Glycation End-Product Formation with Icodextrin and Dextrose

1997 ◽  
Vol 17 (1) ◽  
pp. 52-58 ◽  
Author(s):  
B. Anne ◽  
St. J. Dawnayand ◽  
David J. Millar
Keyword(s):  
Peritoneal Dialysis ◽  
Degradation Products ◽  
Product Formation ◽  
Protein Glycation ◽  
Dialysis Fluid ◽  
Advanced Glycation ◽  
Advanced Glycation End Product ◽  
Glucose Degradation Products ◽  
Peritoneal Dialysis Fluid ◽  
Peritoneal Function

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.

Glucose Degradation Products and Peritoneal Membrane Function

2001 ◽  
Vol 21 (2) ◽  
pp. 201-207 ◽  
Author(s):  
Janusz Witowski ◽  
Thorsten O. Bender ◽  
Gerhard M. Gahl ◽  
Ulrich Frei ◽  
Achim Jörres
Keyword(s):  
Peritoneal Dialysis ◽  
Cell Viability ◽  
Degradation Products ◽  
Membrane Function ◽  
Peritoneal Mesothelial Cells ◽  
Glucose Degradation Products ◽  
And Function ◽  
The Impact ◽  
Dialysis Fluids

Background The bioincompatibility of peritoneal dialysis fluids (PDF) in current use has been partially attributed to the presence of glucose degradation products (GDPs), which are generated during heat sterilization of PDF. Several of the GDPs have been identified and we have recently demonstrated that these GDPs per se may impair the viability and function of human peritoneal mesothelial cells (HPMC) in vitro. It is also possible that GDP-related toxicity is further exacerbated by the milieu of PDF. We review the current literature on GDP and present the results of experiments comparing the impact of heat- and filter-sterilized PDF on the viability and function of HPMC. Methods Peritoneal dialysis fluids with low (1.5%) and high (4.25%) glucose concentrations were laboratory prepared according to the standard formula and sterilized either by heat (H-PDF; 121°C, 0.2 MPa, 20 minutes) or filtration (F-PDF; 0.2 μ). The buildup of GDP was confirmed by UV absorbance at 284 nm. Confluent HPMC monolayers were exposed to these solutions mixed 1:1 with standard M199 culture medium. After 24 hours, cell viability was assessed with the MTT assay, and interleukin-1β–stimulated monocyte chemotactic protein-1 (MCP-1) release with specific immunoassay. Results Exposure of HPMC to H-PDF resulted in a significant decrease in cell viability, with solutions containing 4.25% glucose being more toxic than 1.5% glucose-based PDF (27.4% ± 3.4% and 53.4% ± 11.0% of control values, respectively). In contrast, viability of HPMC exposed to F-PDF was not different from that of control cells. Moreover, treatment with H-PDF impaired the release of MCP-1 from HPMC to a significantly greater degree compared to F-PDF (17.4% and 24.9% difference for low and high glucose PDF, respectively). Conclusions Exposure of HPMC to H-PDF significantly impairs cell viability and the capacity for generating MCP-1 compared to F-PDF. This effect is likely to be mediated by GDPs present in H-PDF but not in F-PDF.

Synergistic cytotoxicity of acidity and glucose degradation products in peritoneal dialysis fluid

2004 ◽  
Vol 7 (3) ◽  
pp. 155-160 ◽  
Author(s):  
Eiji Okabe ◽  
Tadashi Tomo ◽  
Kazuhito Tezono ◽  
Hiroshi Kikuchi ◽  
Jyun-ichi Kadota ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Degradation Products ◽  
Dialysis Fluid ◽  
Glucose Degradation Products ◽  
Synergistic Cytotoxicity ◽  
Peritoneal Dialysis Fluid

Glucose Degradation Products and the Peritoneal Mesothelium

2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 19-22 ◽  
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.

Peritoneal Dialysis Fluid Induces P38-Dependent Inflammation in Human Mesothelial Cells

2011 ◽  
Vol 31 (3) ◽  
pp. 332-339 ◽  
Author(s):  
Andrea Riesenhuber ◽  
Klaus Kratochwill ◽  
Thorsten O. Bender ◽  
Regina Vargha ◽  
David C. Kasper ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Stress Response ◽  
Stress Responses ◽  
Mesothelial Cells ◽  
Hsp70 Expression ◽  
Peritoneal Mesothelial Cells ◽  
P38 Inhibitor ◽  
Peritoneal Dialysis Fluid ◽  
Human Peritoneal Mesothelial Cells ◽  
Ldh Release

BackgroundNoninfectious upregulation of proinflammatory pathways in mesothelial cells may represent an integral part of their stress response upon exposure to peritoneal dialysis fluids (PDF).ObjectiveThe aim of this study was to evaluate the role of the stress-inducible mitogen-activated protein kinase (MAPK) p38 in regulation of inflammatory and stress responses in mesothelial cells following in vitro exposure to PDF.Materials and MethodsHuman peritoneal mesothelial cells were exposed to Dianeal PD4 or Physioneal (Baxter AG, Vienna, Austria) containing 1.36% glucose and then allowed to recover. Phosphorylation of p38, induction of heat shock protein-70 (HSP70), release of lactate dehydrogenase (LDH), secretion of interleukin (IL)-8, gene transcription, and mRNA stability were assessed with and without the MAPK p38 inhibitor SB203580.ResultsExposure to Dianeal resulted in phosphorylation of p38 within 30 minutes (309% of control, p < 0.05) and increased IL-8 release (370% of control, p < 0.05), HSP70 expression (151% of control, p < 0.05), and LDH release (180% of control, p < 0.05). Exposure to Physioneal resulted in attenuated changes in IL-8, HSP70, and LDH. Addition of the p38 inhibitor SB203580 to Dianeal resulted in dampened IL-8 release (-55%; p < 0.05) and basal HSP70 expression, and unchanged LDH release. Effects of p38 on IL-8 were at transcriptional, posttranscriptional, and translational levels.ConclusionThese data confirm concordant p38-dependent upregulation of IL-8 and HSP70 following exposure to bioincompatible PDF. The MAPK p38 pathway therefore links proinflammatory processes and the cellular stress response in human peritoneal mesothelial cells.

scholarly journals Glucose degradation products downregulate ZO-1 expression in human peritoneal mesothelial cells: the role of VEGF

2005 ◽  
Vol 20 (7) ◽  
pp. 1336-1349 ◽  
Author(s):  
Joseph C. K. Leung ◽  
Loretta Y. Y. Chan ◽  
Felix F. K. Li ◽  
Sydney C. W. Tang ◽  
Kwok Wa Chan ◽  
...  
Keyword(s):  
Degradation Products ◽  
Mesothelial Cells ◽  
Peritoneal Mesothelial Cells ◽  
Glucose Degradation Products ◽  
Human Peritoneal Mesothelial Cells
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