In-vitro biocompatibility of alternative CAPD fluids; comparison of bicarbonate-buffered and glucose-polymer-based solutions.
Evidence is accumulating that conventional dialysis fluids for CAPD are incompatible with peritoneal host defence. We therefore investigated the effect of alternative CAPD fluids on mononuclear leukocyte (PBMC) viability and cytokine production in vitro. Fluids tested were bicarbonate-buffered solutions containing 1.5% or 4.25% glucose, 7.5% glucose polymer dialysis fluid (GPDF), and conventional 1.5% glucose fluid (G1.5%). PBMC were stimulated (2 h, 37 degrees C) in the different test fluids with a clinical isolate of Staphylococcus epidermidis or Escherichia coli lipopolysaccharide. The cytokines TNF alpha and IL-6 in PBMC supernatants were measured by specific enzyme immunoassays. Induction of cytokine messenger RNA was evaluated by reverse transcription-polymerase chain reaction. Conventional G1.5% (pH 5.5) inhibited cytokine release from activated PBMC by > 95%, whereas cell responses in low-glucose bicarbonate fluid were not significantly reduced. In contrast, high-glucose bicarbonate fluid exerted > 80% inhibition despite its neutral pH. GPDF was inhibitory at its initial low pH, whereas cytokine release was restored following pH neutralization. Cytokine mRNA expression was suppressed by conventional G1.5% fluid and by high-glucose bicarbonate fluid. These data indicate that pH neutralization leads to a substantial improvement of dialysis fluid biocompatibility; however, hyperosmolality and/or high glucose content inhibit cell responsiveness even at normal pH. Replacement of glucose by glucose polymer might prove beneficial provided that the initial low pH is neutralized.
Department of Nephrology, Universitätsklinikum Rudolf Virchow, Berlin-Charlottenburg, Germany.
A
A
Jörres
G M
GM
Gahl
N
N
Topley
A
A
Neubauer
K
K
Ludat
C
C
Müller
J
J
Passlick-Deetjen
D000199:Actins / Q000235:genetics; D001483:Base Sequence; D001639:Bicarbonates / Q000737:chemistry; D002021:Buffers; D002470:Cell Survival / Q000187:drug effects; D015314:Dialysis Solutions / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005936:Glucans / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008969:Molecular Sequence Data; D010531:Peritoneal Dialysis, Continuous Ambulatory; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000199:Actins; D001639:Bicarbonates; D002021:Buffers; D015314:Dialysis Solutions; D005936:Glucans; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose