scholarly journals Peritoneal dialysis with solutions low in glucose degradation products is associated with improved biocompatibility profile towards peritoneal mesothelial cells

2004 ◽  
Vol 19 (4) ◽  
pp. 917-924 ◽  
Author(s):  
J. Witowski ◽  
K. Korybalska ◽  
K. Ksiazek ◽  
J. Wisniewska-Elnur ◽  
A. Jorres ◽  
...  
2001 ◽  
Vol 12 (11) ◽  
pp. 2434-2441 ◽  
Author(s):  
JANUSZ WITOWSKI ◽  
JUSTYNA WISNIEWSKA ◽  
KATARZYNA KORYBALSKA ◽  
THORSTEN O. BENDER ◽  
ANDRZEJ BREBOROWICZ ◽  
...  

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.


2001 ◽  
Vol 21 (2) ◽  
pp. 201-207 ◽  
Author(s):  
Janusz Witowski ◽  
Thorsten O. Bender ◽  
Gerhard M. Gahl ◽  
Ulrich Frei ◽  
Achim Jörres

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.


2008 ◽  
Vol 28 (3_suppl) ◽  
pp. 123-127
Author(s):  
Tadashi Tomo

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.


2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 19-22 ◽  
Author(s):  
Achim Jörres ◽  
Thorsten O. Bender ◽  
Janusz Witowski

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.


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 ◽  
...  

2007 ◽  
Vol 107 (1) ◽  
pp. c26-c34 ◽  
Author(s):  
Mohamed-Saiel Saeed Alhamdani ◽  
Abdul-Hameed A.-M. Al-Kassir ◽  
Fawzi K.H. Abbas ◽  
Nidham A. Jaleel ◽  
Maha F. Al-Taee

2001 ◽  
Vol 21 (6) ◽  
pp. 607-610 ◽  
Author(s):  
Torbjörn Linden ◽  
Barbara Musi ◽  
Lena Järkelid ◽  
Gunita Forsbäck ◽  
Per Kjellstrand ◽  
...  

Objective When peritoneal dialysis (PD) fluids are heat sterilized, glucose is degraded to carbonyl compounds. These compounds are known to interfere with many cellular functions and to promote the formation of advanced glycation end-products. However, little is known about what actually happens with glucose degradation products (GDPs) after infusion into the peritoneal cavity. The aim of the present study was to investigate possible targets for GDPs in the peritoneal cavity. Design In vitro reactions between residual fluid and GDPs were studied by incubating unused PD fluid with overnight dialysate. Confluent monolayer cultures of human mesothelial cells were used as a model to study the reactions of GDPs with the cells lining the peritoneal cavity. Methods Samples were analyzed, using high pressure liquid chromatography, for the presence of formaldehyde, acetaldehyde, 5-hydroxymethyl-2-furaldehyde (5-HMF), methylglyoxal, and 3-deoxyglucosone (3-DG). Cytotoxicity was determined as inhibition of proliferation of cultured fibroblasts. Results None of the analyzed GDPs reacted with overnight dialysate. Formaldehyde and methylglyoxal, in contrast to 3-DG and 5-HMF, reacted with the cultured mesothelial cells. Conclusions Low molecular weight carbonyls such as formaldehyde and methylglyoxal most probably react with the mesothelial cells lining the peritoneal cavity, and could be responsible for the disappearance of these cells during long-term treatment. 3-Deoxyglucosone showed remarkably low reactivity and was most probably transported within the patient.


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