Prolonged exposure to glucose degradation products impairs viability and function of human peritoneal mesothelial cells.
Bioincompatibility of peritoneal dialysis fluids (PDF) has been linked to the presence of glucose degradation products (GDP). Previous experiments have shown that short-term exposure to several GDP at concentrations found in commercially available PDF had no significant effect on human peritoneal mesothelial cells (HPMC). During continuous ambulatory peritoneal dialysis, however, cells are continually exposed to GDP for extended periods of time. Thus, the impact of GDP on HPMC during long-term exposure was assessed. HPMC were cultured for up to 36 d in the presence of 6 identified GDP (acetaldehyde, formaldehyde, furaldehyde, glyoxal, methylglyoxal, and 5-HMF) at doses that reflect their concentrations in conventional PDF. At regular time intervals, the ability of HPMC to secrete cytokines (interleukin-6 [IL-6]) and extracellular matrix molecules (fibronectin) was evaluated. In addition, cell viability, morphology, and proliferative potential were assessed. Exposure to GDP resulted in a significant reduction in mesothelial IL-6 and fibronectin release. Approximately 80% of this decrease occurred during the first 12 d of the exposure and was paralleled by a gradual loss of cell viability and development of morphologic alterations. After 36 d of exposure, the number of cells in GDP-treated cultures was reduced by nearly 60%. However, GDP-treated cells were able to resume normal proliferation when transferred to a normal GDP-free medium. HPMC viability and function may be impaired during long-term exposure to clinically relevant concentrations of GDP, which suggests a potential role of GDP in the pathogenesis of peritoneal membrane dysfunction during chronic peritoneal dialysis.
Witowski
Janusz
J
Department of Nephrology and Medical Intensive Care, Universitätsklinikum Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Berlin, Germany.|Department of Pathophysiology, University Medical School, Poznañ, Poland.
Wisniewska
Justyna
J
Department of Pathophysiology, University Medical School, Poznañ, Poland.
Korybalska
Katarzyna
K
Department of Pathophysiology, University Medical School, Poznañ, Poland.
Bender
Thorsten O
TO
Department of Nephrology and Medical Intensive Care, Universitätsklinikum Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Berlin, Germany.
Breborowicz
Andrzej
A
Department of Pathophysiology, University Medical School, Poznañ, Poland.
Gahl
Gerhard M
GM
Department of Nephrology and Medical Intensive Care, Universitätsklinikum Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Berlin, Germany.
Frei
Ulrich
U
Department of Nephrology and Medical Intensive Care, Universitätsklinikum Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Berlin, Germany.
Passlick-Deetjen
Jutta
J
Fresenius Medical Care, Bad Homburg, Germany.
Jörres
Achim
A
Department of Nephrology and Medical Intensive Care, Universitätsklinikum Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Berlin, Germany.
D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008970:Molecular Weight; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D013997:Time Factors
D000447:Aldehydes; D003470:Culture Media; D005353:Fibronectins; D015850:Interleukin-6; D005947:Glucose