title: Mesothelial toxicity of peritoneal dialysis fluids is related primarily to glucose degradation products, not to glucose per se.
abstract: OBJECTIVE
  High concentrations of glucose and/or formation of glucose degradation products (GDPs) during heat sterilization of peritoneal dialysis fluids (PDFs) are believed to be key factors in the limited biocompatibility of PDFs. We have previously shown that several identified GDPs can specifically impair human peritoneal mesothelial cell (HPMC) function. In the present study we aimed at differentiating the respective roles of glucose and GDPs in the toxicity of PDF to mesothelial cells.
  
  
  METHODS
  HPMCs were acutely pre-exposed to or incubated chronically in the presence of pH-neutral PDF sterilized by either heat (H-PDF) or filtration (F-PDF). In addition, HPMCs were treated with commercially available H-PDF manufactured either conventionally, that is, in single-chamber containers, or using novel dual-chamber bags that help to substantially decrease GDP formation. Functional assessment of HPMCs included viability, release of interleukin (IL)-6, and proliferation.
  
  
  RESULTS
  Viability and release of IL-6 from HPMCs pretreated with H-PDF (pH 7.3) for 1 to 4 hours were significantly reduced compared to cells exposed to corresponding F-PDF. Incubation in medium mixed (1:1) with H-PDF considerably impaired growth of HPMCs, and over a period of 10 days gradually decreased both the viability of HPMCs and their ability to generate IL-6. These effects were either absent from or significantly less in HPMCs exposed to F-PDF. Similar differences were observed when commercial GDP-containing H-PDFs were compared with newly designed H-PDFs free of GDPs.
  
  
  CONCLUSIONS
  Impaired viability and function of HPMCs exposed to glucose-containing pH-neutral PDF is related predominantly to the presence of GDP and, to a significantly lesser extent, to the presence of glucose per se. Prevention of GDP formation during autoclaving markedly improves the biocompatibility of H-PDF with HPMCs.
authors.affiliation: Department of Nephrology and Medical Intensive Care, Universitätsklinikum Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Germany.
authors.forename: Janusz
authors.initials: J
authors.lastname: Witowski
authors.forename: Thorsten O
authors.initials: TO
authors.lastname: Bender
authors.forename: Justyna
authors.initials: J
authors.lastname: Wisniewska-Elnur
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Ksiazek
authors.forename: Jutta
authors.initials: J
authors.lastname: Passlick-Deetjen
authors.forename: Andrzej
authors.initials: A
authors.lastname: Breborowicz
authors.forename: Achim
authors.initials: A
authors.lastname: Jörres
mesh_terms: D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000009:adverse effects*; D004847:Epithelial Cells / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism* / Q000633:toxicity*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D010530:Peritoneal Dialysis / Q000379:methods; D010537:Peritoneum / Q000187:drug effects*
chemical_list: D015314:Dialysis Solutions; D015850:Interleukin-6; D005947:Glucose