Peritoneal defence in peritoneal dialysis

Abstract

Summary: Over the past 20 years the use of peritoneal dialysis as a renal replacement therapy has increased dramatically. Its use has identified that infection and long‐term loss of function of the peritoneal membrane as a dialysing organ are the major problems associated with this form of therapy. This has led, over the last decade, to research into the importance of peritoneal host defence mechanisms in the control of infection and more recently to studies on the contribution of the resident peritoneal cell populations (peritoneal macrophages; PMO) and the cells of the peritoneal membrane (mesothelial cells and peritoneal fibroblasts) to the ‘peritoneal cytokine network’. It is widely accepted that PMO represent the first line of cellular defence against peritoneal infection. Recently it has become clear that the cells of the peritoneal membrane, and the mesothelial cell in particular, are primary responders in the inflammatory cascade. Evidence suggests that the initial activation of inflammation occurs on the peritoneal membrane and that the mesothelium and PMO interact directly (via adhesion molecule/integrin binding) and indirectly via the secretion of pro‐/anti‐ and immuno‐modulatory mediators to initiate, amplify and resolve inflammatory episodes. In vitro studies of peritoneal cell inflammatory function have been paralleled by ex vivo observations of the peritoneal inflammatory cascade. These have identified the temporal sequence of inflammatory events (cytokine and prostaglandin synthesis) that occur in vivo. These observations demonstrate that local (intra‐peritoneal) generation of inflammatory mediators and confirm the importance of the various peritoneal cell populations and the cross‐talk between them in the evolution of the inflammatory response. the initial activation appears to occur on the mesothelial cell surface driven by the pro‐inflammatory products of the PMO (IL‐1 and tumour necrosis factor; TNF). This results in the amplification of the inflammatory cascade and the generation of chemotactic cytokines (IL‐8 and MCP‐i) responsible for the recruitment of inflammatory leucocytes (neutrophils, macrophages and lymphocytes) into the peritoneal cavity. This process is facilitated by the simultaneous up‐regulation of adhesion molecules (intercellular adhesion molecule‐1; ICAM‐1 and vascular cell adhesion molecule‐1; VCAM‐1) on the mesothelial cell surface which facilitate the transmigration of leucocytes across the peritoneal membrane. Taken together these data suggest that both leucocyte and peritoneal membrane cell populations, interact and play pivotal roles in the control of peritoneal defence during continuous ambulatory peritoneal dialysis.