3,4-DGE in Peritoneal Dialysis Fluids Cannot be Found in Plasma after Infusion into the Peritoneal Cavity

2008 ◽  
Vol 28 (3) ◽  
pp. 277-282 ◽  
Author(s):  
Martin Erixon ◽  
Anders Wieslander ◽  
Torbjörn Lindén ◽  
Ola Carlsson ◽  
Jan Åke Jönsson ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Human Plasma ◽  
Peritoneal Cavity ◽  
Degradation Products ◽  
High Reactivity ◽  
The Other ◽  
Glucose Degradation Products ◽  
Pass Through ◽  
Dialysis Fluids

Objective Glucose degradation products (GDPs) are important in the outcome of peritoneal dialysis (PD) treatment. 3,4-dideoxyglucosone-3-ene (3,4-DGE) is the most cytotoxic GDP found in conventionally manufactured fluids and may, in addition, be recruited from 3-deoxyglucosone (3-DG). It is not known what happens with those GDPs in patients during PD. The aim of this study was to investigate if the 3,4-DGE and 3-DG in PD fluids can be found in plasma during treatment. Design PD patients were dialyzed with a conventional PD fluid containing 43 μmol/L 3,4-DGE and 281 μmol/L 3-DG. Parallel experiments were performed in rats as well as in vitro with human plasma. The rats were dialyzed with a PD fluid containing 100 μmol/L 3,4-DGE and 200 μmol/L 3-DG. Results The concentration of 3,4-DGE in the peritoneum decreased at a much higher rate than 3-DG during the dwell. 3,4-DGE was not, however, detected in the plasma of patients or rats during dialysis. The concentration of 3-DG in plasma peaked shortly after infusion of the fluid to the peritoneal cavity. The concentration of 3,4-DGE during experimental incubation in plasma decreased rapidly, while the concentration of 3-DG decreased only 10% as rapidly or less. Conclusion 3,4-DGE could not be detected in plasma from either PD patients or rats during dialysis. This is presumably due to its high reactivity. 3-DG may, on the other hand, pass through the membrane and be detected in the blood.

3,4-Dideoxyglucosone-3-Ene in Peritoneal Dialysis Fluids Infused into the Peritoneal Cavity Cannot be Found in Plasma

2009 ◽  
Vol 29 (2_suppl) ◽  
pp. 28-31 ◽  
Author(s):  
Martin Erixon ◽  
Anders Wieslander ◽  
Torbjörn Lindén ◽  
Ola Carlsson ◽  
Jan Åke Jönsson ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Human Plasma ◽  
Peritoneal Cavity ◽  
Degradation Products ◽  
High Reactivity ◽  
The Other ◽  
Glucose Degradation Products ◽  
Pass Through ◽  
Dialysis Fluids

Objective Glucose degradation products (GDPs) are important for the outcome of peritoneal dialysis (PD) treatment. The most cytotoxic GDP found in conventionally manufactured fluids, 3,4-dideoxyglucosone-3-ene (3,4-DGE), may in addition be recruited from 3-deoxyglucosone (3-DG). What happens with the GDPs in the fluid infused into patients during PD is not known. We investigated whether 3,4-DGE and 3-DG in PD fluid can be found in plasma during treatment. Design Patients on PD were dialyzed with a conventional PD fluid containing 43 μmol/L 3,4-DGE and 281 μmol/L 3-DG. Parallel experiments were performed in rats and in vitro with human plasma. The rats were dialyzed with a PD fluid containing 100 μmol/L 3,4-DGE and 200 μmol/L 3-DG. Results The 3,4-DGE concentration in the peritoneum declined at a much higher rate during the dwell than did the 3-DG concentration. However, 3,4-DGE was not detected in the plasma of patients or of rats during dialysis. The 3-DG concentration in plasma peaked shortly after infusion of fluid into the peritoneal cavity. The 3,4-DGE concentration during experimental incubation in plasma declined rapidly; the 3-DG concentration declined only 10% as rapidly (or less). Conclusion During dialysis, 3,4-DGE could not be detected in plasma of either PD patients or rats, presumably because of its high reactivity. On the other hand, 3-DG may pass through the membrane and be detected in the blood.

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.

Glucose Degradation Products in Peritoneal Dialysis Fluids: How they can be Avoided

2001 ◽  
Vol 21 (3_suppl) ◽  
pp. 119-124 ◽  
Author(s):  
Anders Wieslander ◽  
Torbjörn Linden ◽  
Per Kjellstrand
Keyword(s):  
Peritoneal Dialysis ◽  
Degradation Products ◽  
Low Ph ◽  
Relative Importance ◽  
In Vitro Methods ◽  
Glucose Degradation Products ◽  
Peritoneal Tissue ◽  
In Vitro Inhibition ◽  
Dialysis Fluids

♦ Objectives A patient on peritoneal dialysis (PD) uses 3 – 7 tons of PD fluid every year. The result is considerable stress on the peritoneal tissue. Aspects of PD fluids that have been considered responsible for bioincompatibility are low pH, high osmolality, high glucose and lactate concentrations, and the presence of glucose degradation products (GDPs). However, the relative importance of each factor in PD fluid has so far not been investigated. Discovering their relative importance was the aim of the present study. ♦ Methods Two main methods for investigating biocompatibility were used in this study: cytotoxicity measured as in vitro inhibition of cell growth, and in vitro AGE formation measured as albumin-linked fluorescence. ♦ Results The two most important factors for determining in vitro bioincompatibility of PD fluids were the presence of GDPs, which caused both severe cytotoxicity and strong AGE promotion, and low pH, which induced severe cytotoxicity. ♦ Conclusions The biocompatibility of PD fluids can be monitored through fairly simple in vitro methods such as cell proliferation and AGE formation. Bioincompatibility of PD fluids is caused mainly by the presence of GDPs and low pH. These findings correlate well with known clinical bioincompatibility.

Glucose Degradation Products in Peritoneal Dialysis Fluids May Have Both Local and Systemic Effects: A Study of Residual Fluid and Mesothelial Cells

2001 ◽  
Vol 21 (6) ◽  
pp. 607-610 ◽  
Author(s):  
Torbjörn Linden ◽  
Barbara Musi ◽  
Lena Järkelid ◽  
Gunita Forsbäck ◽  
Per Kjellstrand ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Cavity ◽  
Degradation Products ◽  
Term Treatment ◽  
Mesothelial Cells ◽  
Cultured Fibroblasts ◽  
Inhibition Of Proliferation ◽  
Glucose Degradation Products ◽  
Long Term Treatment

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.

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.

In Vitro Biocompatibility of a Heat -Sterilized, Low Toxic, and Less Acidic Fluid for Peritoneal Dialysis

1995 ◽  
Vol 15 (2) ◽  
pp. 158-164 ◽  
Author(s):  
Anders P. Wieslander ◽  
Reinhold Deppisch ◽  
Eva Svensson ◽  
Gunita Forsbäck ◽  
Rose Speidel ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
High Performance ◽  
Mononuclear Cells ◽  
Degradation Products ◽  
Fibroblast Cell ◽  
Interleukin 1Β ◽  
Uv Absorbance ◽  
Glucose Degradation Products ◽  
In Vitro Biocompatibility

Objective The aim of this study was to investigate a peritoneal dialysis (PD) fluid (PD-Bio), produced with the intention of reducing the amount of glucose degradation products and to increase the final pH. The heat sterilization of the fluid was performed with the glucose separated from the electrolytes. After sterilization the two solutions were combined. Methods The in vitro biocompatibility of PD-Bio was measured as the inhibition of cell growth of a cultured fibroblast cell line and as the stimulated release of interleukin-1β from cultured human mononuclear cells. The glucose degradation products were measured as UV absorbance at 228 nm or 284 nm and the concentration of aldehydes was estimated with high-performance liquid chromatography and gas chromatography. Results Our results demonstrate that in comparison to conventional PD fluids the pH of PD-Bio was increased, to about 6.5. Due to less contaminating glucose degradation products in PD-Bio, basal cytotoxicity was significantly decreased for both 1.5% and 4% glucose-containing fluids, and the stimulated release of interleukin-1β was normalized compared to sterile filtered controls with the same pH. UV absorbance measured at 228 nm was decreased, whereas the absorbance at 284 nm was equal to that of a conventional fluid. In PD-Bio the concentrations of formaldehyde, acetaldehyde, methylglyoxal, and 2-furaldehyde were found to be below the detection limit, whereas glyoxal was present in the same and 5hydroxymethylfurfural (5-HMF) in higher concentrations than in conventionally produced PD fluid. Conclusions The results demonstrate that it is possible to improve biocompatibility of PD fluids by simply changing the way the fluid is produced.

scholarly journals Glucose degradation products in peritoneal dialysis fluids: Do they harm?

2003 ◽  
Vol 63 ◽  
pp. S148-S151 ◽  
Author(s):  
Janusz Witowski ◽  
Achim Jörres ◽  
Katarzyna Korybalska ◽  
Krzysztof Ksiazek ◽  
Justyna Wisniewska-Elnur ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Degradation Products ◽  
Glucose Degradation Products ◽  
Dialysis Fluids

Are Aldehydes in Heat-Sterllized Peritoneal Dialysis Fluids Toxic in Vitro?

1995 ◽  
Vol 15 (4) ◽  
pp. 348-352 ◽  
Author(s):  
Anders P. Wieslander ◽  
Anders H.G. Andrén ◽  
Carin Nilsson-Thorell ◽  
Natalia Muscalu ◽  
Per T.T. Kjellstrand ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Side Effects ◽  
Cell Growth ◽  
Superoxide Radical ◽  
Degradation Products ◽  
In Vitro Toxicity ◽  
Growth Media ◽  
Cell Growth Inhibition ◽  
Dialysis Fluids

Objective Chemical analysis of several brands of peritoneal dialysis fluids (PD fluids) has revealed the presence of 2-furaldehyde, 5-HMF (5-hydroxymethylfuraldehyde), acetaldehyde, formaldehyde, glyoxal, and methylglyoxal. The aim of this study was to investigate if the in vitro side effects caused by glucose degradation products, mainly formed during heat sterilization, are due to any of these recently identified aldehydes. Design Cell growth media or sterile filtered PD fluids were spiked with different concentrations ofthealdehydes. Measurements In vitro side effects were determined as the inhibition of cell growth of cultured mouse fibro blasts or stimulated superoxide radical release from human peritoneal cells. Results Our results demonstrate that the occurrences of 2-furaldehyde, 5-HMF, acetaldehyde, formaldehyde, glyoxal, or methylglyoxal in heat-sterilized PD fluids are probably not the direct cause of in vitro side effects. In order to induce the same magnitude of cell growth inhibition as the heat-sterilized PD fluids, the concentrations of 2-furaldehyde, glyoxal, and 5-HMF had to be 50 to 350 times higher than those quantified in the PD fluids. The concentrations of acetaldehyde, formaldehyde, and methylglyoxal observed in the heat-sterilized PD fluids were closer to the cytotoxic concentrations although still 3 to 7 times lower. Conclusion Since none of these aldehydes caused in vitro toxicity at the tested concentrations, the toxicity found in PD fluids is likely to be due to another glucose degradation product, not yet identified. However, it is possible that these aldehydes may still have adverse effects for patients on peritoneal dialysis.

Degradation in Peritoneal Dialysis Fluids May be Avoided by Using Low pH and High Glucose Concentration

2001 ◽  
Vol 21 (4) ◽  
pp. 338-344 ◽  
Author(s):  
Per Kjellstrand ◽  
Evi Martinson ◽  
Anders Wieslander ◽  
Karin Kjellstrand ◽  
Elin Jeppsson ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Glucose Concentration ◽  
Degradation Products ◽  
Heating Time ◽  
Uv Absorbance ◽  
High Concentration ◽  
Number Of Factors ◽  
Initial Ph ◽  
Dialysis Fluids

Objective When glucose is present in a medical fluid, the heat applied during sterilization leads to degradation. The glucose degradation products (GDPs) give rise to bioincompatible reactions in peritoneal dialysis patients. The extent of the degradation depends on a number of factors, such as heating time, temperature, pH, glucose concentration, and catalyzing substances. In the present work, we investigated the influence of pH and concentration in order to determine how to decrease the amounts of GDPs produced. Design Glucose solutions (1% - 60% glucose; pH 1 - 8) were heat sterilized at 121°C. Ultraviolet (UV) absorption, aldehydes, pH, and inhibition of cell growth (ICG) were used as measures of degradation. Results Glucose degradation was minimum at an initial pH (prior to sterilization) of around 3.5 and at a high concentration of glucose. There was considerable development of acid degradation products during the sterilization process when the initial pH was high. Two different patterns of development of UV-absorbing degradation products were seen: one below pH 3.5, dominated by the formation of 5-hydroxy-methyl-2-furaldehyde (5-HMF); and one above, dominated by degradation products absorbing at 228 nm. 3-Deoxyglucosone (3-DG) concentration and the portion of 228 nm UV absorbance not caused by 5-HMF were found to relate to the in vitro bioincompatibility measured as ICG; there was no relation between 5-HMF or absorbance at 284 nm and bioincompatibility. Conclusion In order to minimize the development of bioincompatible GDPs in peritoneal dialysis fluids during heat sterilization, pH should be kept around 3.2 and the concentration of glucose should be high. 5-HMF and 284 nm UV absorbance are not reliable as quality measures. 3-DG and the portion of UV absorbance at 228 nm caused by degradation products other than 5-HMF seem to be reliable indicators of bioincompatibility.

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