Glucose-based PD solution, but not icodextrin-based PD solution, induces plasminogen activator inhibitor-1 and...

Peritoneal dialysis (PD) solutions containing glucose are considered to cause peritoneal fibrosis. Plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) participate in fibrogenesis of various organs, and human peritoneal mesothelial cells (HPMC) can produce PAI-1 and t-PA following glucose stimulation. Icodextrin has been widely used as an alternative osmotic agent. In this study, we investigated whether icodextrin-based PD solution reduced the production of PAI-1 and t-PA by HPMC. We also examined the involvement of extracellular signal-regulated kinase 1/2 (ERK1/2). Glucose-based PD solutions increased the production of PAI-1 and t-PA by HPMC, whereas icodextrin-based PD solution exerted lesser effects. Glucose-based PD solutions activated ERK1/2, and PD98059 inhibited the production of PAI-1 and t-PA-responses not observed with icodextrin-based PD solution. In conclusion, glucose-based PD solutions, unlike icodextrin-based PD solution, induce overproduction of PAI-1 and t-PA via the ERK1/2 pathway.