Glucose degradation products and peritoneal membrane function

Background:The bioincompatibility of peritoneal dialysis fluids (PDF) in cu rrent use has been partially attributed to the presence of glucose degradat ion products (GDPs), which are generated during heat sterilization of PDF. Several of the GDPs have been identified and we have recently demonstrated that these GDPs per se may impair the viability and function of human perit oneal mesothelial cells (HPMC) in vitro. It is also possible that GDP-relat ed toxicity is further exacerbated by the milieu of PDF. We review the curr ent literature on GDP and present the results of experiments comparing the impact of heat- and filter-sterilized PDF on the viability and function of HPMC. Methods: Peritoneal dialysis fluids with low (1.5%) and high (4.25%) glucos e concentrations were laboratory prepared according to the standard formula and sterilized either by heat (H-PDF; 121 degreesC, 0.2 MPa, 20 minutes) o r filtration (F-PDF; 0.2 mu). The buildup of GDP was confirmed by UV absorb ance at 284 nm. Confluent HPMC monolayers were exposed to these solutions m ixed 1:1 with standard M199 culture medium. After 24 hours, cell viability was assessed with the MTT assay, and interleukin-1 beta -stimulated monocyt e chemotactic protein-1 (MCP-1) release with specific immunoassay. Results: Exposure of HPMC to H-PDF resulted in a significant decrease in ce ll viability, with solutions containing 4.25% glucose being more toxic than 1.5% glucose-based PDF (27.4% +/- 3.4% and 53.4% +/- 11.0% of control valu es, respectively). In contrast, viability of HPMC exposed to F-PDF was not different from that of control cells. Moreover, treatment with H-PDF impair ed the release of MCP-1 from HPMC to a significantly greater degree compare d to F-PDF (17.4% and 24.9% difference for low and high glucose PDF, respec tively). Conclusions: Exposure of HPMC to H-PDF significantly impairs cell viability and the capacity for generating MCP-1 compared to F-PDF. This effect is li kely to be mediated by GDPs present in H-PDF but not in F-PDF.