Glycosaminoglycans and the peritoneum

Abstract

The introduction of peritoneal dialysis (PD) over two decades ago has allowed us to manipulate the peritoneal membrane to perform as a continuous dialysing organ. To maximize the efficacy of solute transport and waste removal, conventional PD fluids require unphysiological concentrations of glucose to provide the osmotic drive, lactate to alleviate metabolic acidosis, and a low pH to prevent the caramelization of glucose during the preparation of the solutions. These factors either alone or in combination, are irritants to the peritoneal membrane. Thus, continuous exposure of the peritoneum to PD solutions, together with frequent episodes of peritonitis confers a chronic inflammatory response within the peritoneum. It is, therefore, not unexpected that with time, long-term PD patients develop structural and functional changes within the peritoneum, which in many cases develop into peritoneal fibrosis of varying degrees and compromises the peritoneal membrane as a dialysing organ. To date, numerous studies have investigated methods to improve the efficiency of PD and preserve the structure of the peritoneal membrane. Recently, a number of reports have documented the beneficial effects of intraperitoneal administration of glycosaminoglycans (GAGs) on both the structural and functional qualities of the peritoneum. In this context, GAGs have been demonstrated to inhibit collagen synthesis within the peritoneum, decrease peritoneal advanced glycosylated end-products (AGE) deposition, and modulate cytokine and growth factor synthesis. This review will examine the available data with regards to the potential role of GAGs in maintaining ultrafiltration, solute transport and the structural integrity of the peritoneum.