Molecular pathways in peritoneal fibrosis

Peritoneal dialysis (PD) is a renal replacement therapy for patients with end-stage renal disease that is equivalent to hemodialysis with respect to adequacy, mortality, and other outcome parameters, yet providing superior quality-of-life measures and cost savings. However, long-term usage of the patient's peritoneal membrane as a dialyzer filter is unphysiological and leads to peritoneal fibrosis, which is a major factor of patient morbidity and PD technique failure, resulting in a transfer to hemodialysis or death. Peritoneal fibrosis pathophysiology involves chronic inflammation and the fibrotic process itself. Frequently, inflammation precedes membrane fibrosis development, although a bidirectional relationship of one inducing the other exists. This review aims at highlighting the histopathological definition of peritoneal fibrosis, outlining the interplay of fibrosis, angiogenesis and epithelial-to-mesenchymal transition (EMT), delineating important fibrogenic pathways involving Smad-dependent and Smad-independent transforming growth factor-β (TGF-β) as well as connective tissue growth factor (CTGF) signaling, and summarizing historic and recent studies of inflammatory pathways involving NOD-like receptor protein 3 (NLRP3)/interleukin (IL)-1β, IL-6, IL-17, and other cytokines.