Causes and mechanisms of peritoneal fibrosis and possible application of NF-κB inhibitor for prevention and treatment

Peritoneal dialysis is an established form of the renal replacement therapy in patients with end stage renal failure. Continuous Ambulatory Peritoneal Dialysis developed by Moncrief and Popovich in 1975 was a revolutionary event, and contributed much to wide application of that form of treatment in uremic patients. On the other hand, the weak point of peritoneal dialysis is relatively short viability of the peritoneum as the dialysis membrane. Two main peritoneal pathologies are observed in patients treated with that form of renal replacement therapy: neovascularization of the membrane what causes increased peritoneal permeability to osmotic solutes and ultrafiltration failure, and fibrosis which results also in ultrafiltration failure due to its decreased hydraulic conductivity and reduced permeability to uremic toxins. Meanwhile, an NF-κB inhibitor DHMEQ was discovered in 2000 and has been successfully used to suppress various inflammatory and neoplastic disease models. NF-κB is likely to be involved in the mechanism of peritoneal inflammation and fibrosis. We have studied whether DHMEQ would inhibit cellular model of peritoneal inflammation and fibrosis. It inhibited inflammatory cytokine and collagen productions in primary culture of human peritoneal mesothelial cells, and intraperitoneal administration of NF-κB inhibitors would be useful to suppress peritoneal fibrosis.