+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found

      Effects of New Peritoneal Dialysis Solutions on Leukocyte Recruitment in the Rat Peritoneal Membrane

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Objectives: Peritonitis remains a principal cause of dropout in peritoneal dialysis (PD). The physiological host response to a peritoneal infection involves a rise in numbers of circulating leukocytes to the peritoneal cavity. We evaluated the effects of (1) conventional peritoneal dialysis fluid (PDF), (2) bicarbonate-based PDF, low in glucose degradation products, and (3) non-glucose PDF on peritoneal leukocyte recruitment in response to an inflammatory stimulus using intravital microscopy. Methods: The visceral peritoneum was exposed to EBSS, conventional lactate-buffered and bicarbonate/lactate-buffered glucose-based PDF and three lactate-buffered non-glucose PDF – icodextrin, amino acid-based PDF and amino acid/glycerol-based PDF. The number of rolling, adhering and extravasated leukocytes and leukocyte rolling velocity was assessed at different time intervals after stimulation with lipopolysaccharide (LPS). Results: Exposure to LPS dissolved in EBSS dramatically increased the number of rolling, adhering and extravasated leukocytes and decreased leukocyte rolling velocity. Conventional PDF completely abolished LPS-induced leukocyte recruitment. Bicarbonate/lactate-buffered PDF only minimally affected the process of leukocyte recruitment, whereas icodextrin PDF resulted in partial inhibition of the immune response. The amino acid-based and the amino acid/glycerol-based PDF inhibited leukocyte recruitment to a similar extent as conventional PDF. Conclusions: Bicarbonate/lactate-buffered PDF has superior biocompatibility towards peritoneal host defense, in spite of its high glucose concentrations. Lactate-buffered non-glucose containing PDF has substantial inhibitory effects on leukocyte recruitment, indicating that the bioincompatibility of high lactate concentrations and/or low pH may not be underestimated.

          Related collections

          Most cited references 15

          • Record: found
          • Abstract: found
          • Article: not found

          Effects of conventional and new peritoneal dialysis fluids on leukocyte recruitment in the rat peritoneal membrane.

          Peritonitis remains an important cause of morbidity and technique failure in peritoneal dialysis (PD). Conventional peritoneal dialysate fluids (PDF) inhibit peritoneal leukocyte function in vitro and may thus adversely affect the immune response to peritonitis. New PDF have been designed with neutral pH, low glucose degradation product (GDP) contents, and bicarbonate as buffer. The present intravital microscopy study examined the effects of conventional and new PDF on leukocyte behavior in the peritoneal microcirculation of Wistar rats. The visceral peritoneum was superfused by a control solution (EBSS), a conventional (CAPD), or a new bicarbonate-buffered PDF with neutral pH and low GDP content (CAPD BicaVera). In addition, spent conventional and new PDF were tested. The number of rolling, adhering, and extravasated leukocytes and leukocyte rolling velocity were assessed at different time intervals after exposure to lipopolysaccharide (LPS) or cell-free supernatants of coagulase-negative staphylococci (CNS-CFS). Exposure to LPS or CNS-CFS dissolved in EBSS dramatically increased the number of rolling, adhering and extravasated leukocytes and decreased leukocyte rolling velocity. Superfusion by CAPD abolished the LPS- or CNS-CFS-induced leukocyte recruitment, whereas CAPD BicaVera had significantly fewer depressant effect. Spent PDF affected the leukocyte response in a similar way as fresh PDF. High lactate concentrations, GDP, and hypertonicity appeared to be mainly responsible for the inhibition of leukocyte recruitment. In conclusion, conventional PDF abolish in vivo leukocyte recruitment in response to potent inflammatory stimuli. Bicarbonate-buffered pH-neutral PDF with low GDP contents have fewer depressant effects and may therefore contribute to a better preservation of peritoneal host defense.
            • Record: found
            • Abstract: found
            • Article: not found

            Glucose-mediated induction of TGF-beta 1 and MCP-1 in mesothelial cells in vitro is osmolality and polyol pathway dependent.

            Glucose is converted to sorbitol and then to fructose via the polyol pathway that has been implicated in the pathogenesis of organ damage. The contribution of the polyol pathway to mesothelial cell activation has, however, not been fully determined. The effect of increasing glucose concentrations on transforming growth factor-beta 1 (TGF-beta 1) and monocyte chemoattractant protein-1 (MCP-1) secretion by human peritoneal mesothelial cells (HPMC) was examined. The importance of the polyol pathway was identified by its specific inhibition with an aldose reductase inhibitor. Incubation of HPMC with 5 to 100 mmol/L glucose resulted in an induction of aldose reductase mRNA and intracellular sorbitol accumulation accompanied by the induction of TGF-beta 1 and MCP-1 mRNA expression and protein secretion. Mannitol at the same concentrations also induced aldose reductase, TGF-beta 1 and MCP-1 mRNA and protein expression but at a lower level than glucose. Sorbinil dose-dependently reduced both intracellular sorbitol levels (79.8% reduction of 60 mmol/L D-glucose induced intracellular sorbitol with 100 micromol/L sorbinil (N = 3, P < 0.01) and glucose-induced TGF-beta 1 and MCP-1 secretion. Mannitol induced TGF-beta 1 and MCP-1 secretion was not reduced by sorbinil. The addition of 15 to 40 mmol/L sodium lactate, either alone or in the presence of D-glucose enhanced TGF-beta 1 and MCP-1 secretion, which was inhibited by sorbinil. In contrast, sodium pyruvate appeared to antagonize D-glucose-induced TGF-beta 1 and MCP-1 secretion. These data suggest that the polyol pathway and osmolality contribute to the regulation of HPMC function by glucose. Control of polyol pathway activation might reduce glucose-mediated damage to the peritoneal membrane and promote its long-term survival.
              • Record: found
              • Abstract: found
              • Article: not found

              Effect of glucose concentration, osmolality, and sterilization process of peritoneal dialysis fluids on cytokine production by peripheral blood mononuclear cells and polymorphonuclear cell functions in vitro.

              We sought to investigate the effects of high glucose concentration, osmolality, and heat sterilization of peritoneal dialysis fluids on tumor necrosis factor-alpha (TNF-alpha) production by peripheral blood mononuclear cells (PBMC) and polymorphonuclear cell (PMN) functions. Blood samples were obtained from eight healthy volunteers. PBMCs and PMNs were harvested by centrifugation with Ficoll-Hypaque (Sigma, St Louis, MO). PBMC were incubated with an equal volume of test fluids and RPMI for 4 hours (pH equilibrated), followed by incubation for 20 hours in RPMI with or without endotoxin (10 ng/mL). Total TNF-alpha production was measured by radioimmunoassay. PMNs were incubated with pH-adjusted test fluids for 30 minutes. After incubation, phagocytosis was determined by the uptake of 14C-labeled Staphylococcus aureus, oxidative burst by reduction of ferricytochrome C to ferrouscytochrome C on stimulation with phorbol myristate acetate, and enzyme release by measurement of endotoxin-stimulated bactericidal/permeability increasing factor. To study the effects of increasing glucose concentration and osmolality on PBMC and PMN functions, we compared conventional 1.5% Dianeal (1.5%D), (Baxter Healthcare Corp, Deerfield, IL) 2.5% Dianeal (2.5%D), 4.25% Dianeal (4.25%D), and control (RPMI for PBMCs and Hank's balanced salt solution for PMNs). PMNs exposed to 4.25%D exhibited an inhibition of phagocytosis, phorbol myristate acetate (PMA)-stimulated oxidative burst, and bactericidal/permeability increasing factor release compared with control, 1.5%D, or 2.5%D. To study the effects of increased osmolality when controlled for glucose concentration, we compared 1.5%D with 1.5%D in which osmolality was increased to that of 4.25%D with the addition of either sodium chloride (1.5%D+NaCl) or mannitol (1.5%D+M). High osmolality induced higher TNF-alpha production by unstimulated PBMCs and decreased TNF-alpha production by endotoxin-stimulated PBMCs. PMN functions were also inhibited by high osmolality. To study the effects of increased glucose concentration when controlled for osmolality, we compared 4.25%D with 1.5%D+NaCl and 1.5%D+M. High glucose concentration induced an increase in TNF-alpha production by unstimulated PBMCs, a decrease in TNF-alpha production by endotoxin-stimulated PBMCs, and an inhibition of PMN functions. Finally, to investigate the effects of heat sterilization, we compared 4.25%D (heat sterilized) to a filter-sterilized 4.25%D (4.25%D-F). The filter-sterilized fluid induced less changes in PBMC and PMN functions compared with the heat-sterilized fluid. These data suggest that the high glucose concentration, high osmolality, and heat sterilization of peritoneal dialysis fluids adversely affect PBMC and PMN functions. These effects could predispose continuous ambulatory peritoneal dialysis patients to peritonitis, compromise host defense during infection, and jeopardize long-term survival of the peritoneal membrane.

                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                December 2005
                30 August 2005
                : 101
                : 4
                : e139-e145
                aRenal Division, University Hospital, Gent, and bBaxter R&D Europe, Nivelles, Belgium
                87937 Nephron Exp Nephrol 2005;101:e139–e145
                © 2005 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 2, Tables: 3, References: 28, Pages: 1
                Self URI (application/pdf):
                Original Paper

                Cardiovascular Medicine, Nephrology

                Bicarbonate, Icodextrin, Amino acids, Glycerol


                Comment on this article