title: Effect of glucose degradation products on human peritoneal mesothelial cell function.
abstract: Bioincompatibility of conventional glucose-based peritoneal dialysis fluids (PDF) has been partially attributed to the presence of glucose degradation products (GDP) generated during heat sterilization of PDF. Most previous studies on GDP toxicity were performed on animal and/or transformed cell lines, and the impact of GDP on peritoneal cells remains obscure. The short-term effects of six identified GDP on human peritoneal mesothelial cell (HPMC) functions were examined in comparison to murine L929 fibroblasts. Exposure of HPMC to acetaldehyde, formaldehyde, glyoxal, methylglyoxal, furaldehyde, but not to 5-hydroxymethyl-furfural, resulted in dose-dependent inhibition of cell growth, viability, and interleukin-1beta (IL-1beta)-stimulated IL-6 release; for several GDP, this suppression was significantly greater compared with L929 cells. Although the addition of GDP to culture medium at concentrations found in PDF had no major impact on HPMC function, the exposure of HPMC to filter-sterilized PDF led to a significantly smaller suppression of HPMC proliferation compared to that induced by heat-sterilized PDF. The growth inhibition mediated by filter-sterilized PDF could be increased after the addition of clinically relevant doses of GDP. These effects were equally evident in L929 cells. In conclusion, GDP reveal a significant cytotoxic potential toward HPMC that may be underestimated in test systems using L929 cells. GDP-related toxicity appears to be particularly evident in experimental systems using proliferating cells and the milieu of dialysis fluids. Thus, these observations may bear biologic relevance in vivo where HPMC are repeatedly exposed to GDP-containing PDF for extended periods of time.
authors.affiliation: Department of Nephrology and Medical Intensive Care, Universitätsklinikum Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Germany.|Department of Pathophysiology, University Medical School, Poznan, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Witowski
authors.affiliation: Department of Pathophysiology, University Medical School, Poznan, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Korybalska
authors.affiliation: Department of Pathophysiology, University Medical School, Poznan, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Wisniewska
authors.affiliation: Department of Pathophysiology, University Medical School, Poznan, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Breborowicz
authors.affiliation: Department of Nephrology and Medical Intensive Care, Universitätsklinikum Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Germany.
authors.forename: Gerhard M
authors.initials: GM
authors.lastname: Gahl
authors.affiliation: Department of Nephrology and Medical Intensive Care, Universitätsklinikum Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Frei
authors.affiliation: Fresenius Medical Care, Bad Homburg, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Passlick-Deetjen
authors.affiliation: Department of Nephrology and Medical Intensive Care, Universitätsklinikum Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Jörres
mesh_terms: D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D005374:Filtration; D005947:Glucose / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D000093242:Interleukin-6 Inhibitors
chemical_list: D015314:Dialysis Solutions; D005947:Glucose; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors