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PubMedDate not supplied

Glucose degradation products in peritoneal dialysis fluids may have both local and systemic effects: a study of residual fluid and mesothelial cells.

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.

Animals↗

PubMedDate not supplied

3-Deoxyglucosone, a promoter of advanced glycation end products in fluids for peritoneal dialysis.

OBJECTIVE: The accumulation of irreversible formed advanced glycosylation end products (AGE) in the peritoneal cavity might play an important role in the development of ultrafiltration failure and peritoneal membrane destruction. 3-Deoxyglucosone (3-DG), more formally named 3-deoxy-D-erythro-hexos-2-ulose or 3-deoxy-D-erythro-hexosulos is known to be a potent cross-linker responsible for the polymerization of proteins and a precursor of AGE. The purpose of the present study was to determine if the dicarbonyl compound 3-DG, is formed as a glucose degradation product during heat sterilization of fluids for peritoneal dialysis (PD). DESIGN: Four fluids were examined: a commercially available PD fluid Gambrosol (Gambro, Lund, Sweden); Gambrosol-Bio (Gambro), a new PD-fluid produced under conditions that minimize the generation of toxic glucose degradation products; a fluid prepared in the laboratory by sterile-filtration; and a fluid prepared in the laboratory by heat sterilization. METHODS: The concentration of 3-DG was analyzed by measuring the concentration of its diaminonaphthalene derivative by HPLC using a Waters Symmetry C18 column. RESULTS: The 3-DG concentrations in the commercially- and laboratory-prepared heat-sterilized fluids were 118 and 154 micromol/L, respectively. Gambrosol-Bio and the sterile-filtered fluid produced in the laboratory contained 3-DG in concentrations of 12.3 and less than 1.2 micromol/L, respectively. CONCLUSION: Our results demonstrate that during the heat sterilization of conventional PD-fluids, 3-DG is produced as a degradation product of glucose. It was also demonstrated that, through an alteration of the manufacturing condition, the production of 3-DG could be considerably reduced. We speculate that the presence of 3-DG in unused conventional PD-fluid could act as a local promoter, and increase local AGE formation within the peritoneal cavity.

Chromatography, High Pressure Liquid↗