Biological effects of glucose degradation products in peritoneal dialysis fluids
Abstract: Background: It is well known that Peritoneal dialysis (PD) fluids have biological effects on a number of cells and tissues in the peritoneum and the peritoneal cavity. However, little attention has been paid to the influence of glucose degradation products (GDPs), formed during heat-sterilization and storage of PD fluids. Due to the unsaturated carbonyl compounds the GDPs are highly reactive to proteins and nucleic acids. Even if the incidence of peritonitis has decreased over the years, peritonitis remains a major adverse effect of PD and limits the technique survival of this treatment. There is evidence that PD fluids compromise the immune system. The main purpose of the present thesis was thus to study the biological effects of GDPs on the acute inflammatory response of the peritoneum.Experimental design: The effects of GDPs on rolling leukocyte concentration and flow velocity in rat mesenteric microvessels were investigated by vital microscopy. The mesentery was exposed to laboratory made PD fluids with and without GDPs and to a commercial GDP-containing PD fluid. The influence of GDPs on the recruitment of neutrophils to the peritoneal cavity and on the intraperitoneal complement activation in rats was studied after inducing experimental peritonitis with pre-opsonized or untreated zymosan particles suspended in PD fluids. Peritoneal leukocytes were exposed in vitro and in vivo to PD fluids with different contents of GDPs and the respiratory burst response was evaluated by luminol-amplified chemiluminescence. Leukocytes from rats were evaluated after exposure to two laboratory made and two commercial PD fluids with high or low GDP content. Human leukocytes were collected from patients treated with either a conventional GDP containing fluid or a low GDP fluid.Results: GDPs significantly reduced the level of leukocyte rolling adhesion and increased the blood flow velocity in the rat mesentery post-capillary venules. Without affecting the intraperitoneal complement activation, GDPs inhibited the recruitment of neutrophils to the peritoneal cavity significantly during peritonitis induced by opsonized zymosan. GDPs impaired the respiratory burst response of peritoneal phagocytes after in vitro and in vivo exposure to PD fluids in rats and in humans. An increased proportion of necrotic macrophages were detected in patients treated with a conventional high GDP containing fluid compared to a low GDP fluid.Conclusion: The results of the present thesis indicate that GDPs interact with the intravascular adhesion, the recruitment to the peritoneal cavity and the respiratory burst response of neutrophils. By reducing the amount of GDPs in PD fluids the biological effects are reduced and mechanisms important for eliminating an intraperitoneal infection are better preserved in PD patients.
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