Effect of glucose degradation products on human peritoneal mesothelial cell function

Bioincompatibility of conventional glucose-based peritoneal dialysis fluids (PDF) has been partially attributed to the presence of glucose degradation products (GDP);generated during heat sterilization of PDF. Most previous s tudies on GDP toxicity were performed on animal and/or transformed cell lin es, and the impact of GDP on peritoneal cells remains obscure. The short-te rm effects of six identified GDP on human peritoneal mesothelial cell (HPMC ) functions were examined in comparison to murine L929 fibroblasts. Exposur e of HPMC to acetaldehyde, formaldehyde, glyoxal, methylglyoxal, furaldehyd e, but not to 5-hydroxymethyl-furfural, resulted in dose-dependent inhibiti on of cell growth, viability, and interleukin-1 beta (IL-1 beta)-stimulated IL-6 release; for several GDP, this suppression was significantly greater compared with L929 cells. Although the addition of GDP to culture medium at concentrations found in PDF had no major impact on HPMC function, the expo sure of HPMC to filter-sterilized PDF led to a significantly smaller suppre ssion of HPMC proliferation compared to that induced by heat-sterilized PDF . The growth inhibition mediated by filter-sterilized PDF could be increase d after the addition of clinically relevant doses of GDP. These effects wer e equally evident in L929 cells. In conclusion, GDP reveal a significant cy totoxic potential toward HPMC that may be underestimated in test systems us ing L929 cells. GDP-related toxicity appears to be particularly evident in experimental systems using proliferating cells and the milieu of dialysis f luids. Thus, these observations may bear biologic relevance in vivo where H PMC are repeatedly exposed to GDP-containing PDF for extended periods of ti me.