Prolonged exposure to glucose degradation products impairs viability and function of human peritoneal mesothelial cells

Bioincompatibility of peritoneal dialysis fluids (PDF) has been linked to t he presence of glucose degradation products (GDP). Previous experiments hav e shown that short-term exposure to several GDP at concentrations found in commercially available PDF had no significant effect on human peritoneal me sothelial cells (HPMC). During continuous ambulatory peritoneal dialysis, h owever, cells are continually exposed to GDP for extended periods of time. Thus, the impact of GDP on HPMC during long-term exposure was assessed. HPM C were cultured for up to 36 d in the presence of 6 identified GDP (acetald ehyde, formaldehyde, formaldehyde, glyoxal, methylglyoxal, and 5-HMF) at do ses that reflect their concentrations in conventional PDF. At regular time intervals, the ability of HPMC to secrete cytokines (interleukin-6 [IL-6]) and extracellular matrix molecules (fibronectin) was evaluated. In addition , cell viability, morphology, and proliferative potential were assessed. Ex posure to GDP resulted in a significant reduction in mesothelial IL-6 and f ibronectin release. Approximately 80% of this decrease occurred during the first 12 d of the exposure and was paralleled by a gradual loss of cell via bility and development of morphologic alterations. After 36 d of exposure, the number of cells in GDP-treated cultures was reduced by nearly 60%. Howe ver, GDP-treated cells were able to resume normal proliferation when transf erred to a normal GDP-free medium. HPMC viability and function may be impai red during long-term exposure to clinically relevant concentrations of GDP, which suggests a potential role of GDP in the pathogenesis of peritoneal m embrane dysfunction during chronic peritoneal dialysis.