Mesothelial toxicity of peritoneal dialysis fluids is related primarily to glucose degradation products, not to glucose per se

Janusz Witowski, Thorsten O. Bender, Justyna Wisniewska-Elnur, Krzystof Ksiazek, Jutta Passlick-Deetjen, Andrzej Breborowicz, Achim Jörres

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Abstract

◆ Objectives: 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.

Original languageEnglish (US)
Pages (from-to)381-390
Number of pages10
JournalPeritoneal Dialysis International
Volume23
Issue number4
StatePublished - Jul 2003
Externally publishedYes

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Ascitic Fluid
Peritoneal Dialysis
Glucose
Interleukin-6
Hot Temperature

Keywords

  • Biocompatibility
  • Dialysis fluids
  • Glucose degradation products
  • Mesothelial cells

ASJC Scopus subject areas

  • Nephrology

Cite this

Witowski, J., Bender, T. O., Wisniewska-Elnur, J., Ksiazek, K., Passlick-Deetjen, J., Breborowicz, A., & Jörres, A. (2003). Mesothelial toxicity of peritoneal dialysis fluids is related primarily to glucose degradation products, not to glucose per se. Peritoneal Dialysis International, 23(4), 381-390.

Mesothelial toxicity of peritoneal dialysis fluids is related primarily to glucose degradation products, not to glucose per se. / Witowski, Janusz; Bender, Thorsten O.; Wisniewska-Elnur, Justyna; Ksiazek, Krzystof; Passlick-Deetjen, Jutta; Breborowicz, Andrzej; Jörres, Achim.

In: Peritoneal Dialysis International, Vol. 23, No. 4, 07.2003, p. 381-390.

Research output: Contribution to journalArticle

Witowski, J, Bender, TO, Wisniewska-Elnur, J, Ksiazek, K, Passlick-Deetjen, J, Breborowicz, A & Jörres, A 2003, 'Mesothelial toxicity of peritoneal dialysis fluids is related primarily to glucose degradation products, not to glucose per se', Peritoneal Dialysis International, vol. 23, no. 4, pp. 381-390.
Witowski J, Bender TO, Wisniewska-Elnur J, Ksiazek K, Passlick-Deetjen J, Breborowicz A et al. Mesothelial toxicity of peritoneal dialysis fluids is related primarily to glucose degradation products, not to glucose per se. Peritoneal Dialysis International. 2003 Jul;23(4):381-390.
Witowski, Janusz ; Bender, Thorsten O. ; Wisniewska-Elnur, Justyna ; Ksiazek, Krzystof ; Passlick-Deetjen, Jutta ; Breborowicz, Andrzej ; Jörres, Achim. / Mesothelial toxicity of peritoneal dialysis fluids is related primarily to glucose degradation products, not to glucose per se. In: Peritoneal Dialysis International. 2003 ; Vol. 23, No. 4. pp. 381-390.
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AU - Witowski, Janusz

AU - Bender, Thorsten O.

AU - Wisniewska-Elnur, Justyna

AU - Ksiazek, Krzystof

AU - Passlick-Deetjen, Jutta

AU - Breborowicz, Andrzej

AU - Jörres, Achim

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N2 - ◆ Objectives: 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.

AB - ◆ Objectives: 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.

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