Hyaluronan--regulator and initiator of peritoneal inflammation and remodeling

Although previously described as an inert space filler, there is now compelling evidence to underscore the importance of hyaluronan in physiologic and pathologic processes. Despite its simple structure, hyaluronan plays essential roles in embryonic development, phenotypic changes, proliferation, wound healing, inflammation and angiogenesis. Hyaluronan is a major component of the glycocalyx that forms a protective barrier around mesothelial cells, and bestows upon the peritoneal membrane a slippery non-adhesive surface preventing abrasion, infection and tumor dissemination. Hyaluronan is associated with mesothelial-to-mesenchymal transdifferentiation, recruitment of leukocytes to sites of inflammation, and mediates the reparative process after tissue injury by initiating increased synthesis of growth factors. Serum and dialysate levels of hyaluronan are increased in patients maintained on peritoneal dialysis (PD), of which the levels are further increased during episodes of peritonitis. The level of hyaluronan in PD effluents is often used as a surrogate marker for peritoneal inflammation and can predict patient survival. This review will describe the multifaceted roles of hyaluronan in the peritoneum and how these roles are modulated during PD.