Peritoneal mesothelial cells and the extracellular matrix

Abstract

Continuous ambulatory peritoneal dialysis (CARD) is an important treatment for patients with end-stage renal failure. Long-term success is dependent on the functional and structural integrity of the peritoneal membrane. Conventional peritoneal dialysis fluids are non-physiological. They contain glucose at high concentrations to provide the osmotic drive for Ultrafiltration, lactate to correct the metabolic acidosis of renal failure, and a low pH to prevent caramelization of glucose during heat sterilization. These components, in isolation or acting together, exert adverse influences on both the resident cellular and extracellular elements of the peritoneal membrane, as well as phagocytic cells which infiltrate the peritoneum during inflammation, culminating in detrimental structural and functional effects, compromising the viability of the peritoneum during dialysis. Peritoneal biopsy studies of patients on long-term CARD have demonstrated an intercellular space between adjacent mesothelial cells which allows the penetration of peritoneal dialysis fluid into the underlying submesothelium. This, together with episodes of peritonitis, can initiate a chronic inflammatory reaction within the peritoneum characterized by increased synthesis of matrix proteins. Perturbation of the regulatory mechanisms which govern the balance of synthesis and degradation of extracellular matrix can lead to progressive fibrosis. Human peritoneal mesothelial cells (HPMC) have been shown to synthesize fibronectin, laminin, collagens, proteoglycans and hyaluronan in vitro, and thus play a role in the pathogenesis of peritoneal fibrosis. This review will give an overview of extracellular matrix (ECM) synthesis by HPMC, how changes in the synthesis are affected by CAPD and postulate how these changes can compromise the dialytic properties of the peritoneum.