Preventing peritoneal fibrosis - Insights from the laboratory

Abstract

◆ Objective: Peritoneal fibrosis is one of the most serious complications of peritoneal dialysis (PD). Peritoneal fibrosis is characterized by activation of the peritoneal resident cells, accumulation and deposition of excess matrix proteins within the interstitium, and neoangiogenesis and vasculopathy of the peritoneal microvasculature. Compelling evidence now exists to show that elevated glucose concentrations present as the osmotic agent in PD solutions are, per se, responsible for those detrimental changes. Until alternative osmotic agents can fully replace glucose in PD solutions, novel therapeutic strategies are essential to preserve the structural and functional properties of the peritoneum. This review highlights recent experimental data that may offer potential strategies for preservation of the peritoneal structure and improvement of clinical outcome. ◆ Method: Literature review. ◆ Results: Compelling evidence now exists to show that the bioincompatible nature of PD solutions - in particular, elevated glucose concentrations and glucose byproducts - play a pivotal role in the initiation of peritoneal fibrosis. Animal and in vitro studies provide some insight into methods that can potentially be employed to alleviate or retard peritoneal fibrosis. Those methods include use of alterative osmotic agents (polyglucose or amino acids), administration of TGFβ1 antagonists, gene therapy, and pharmacologic interventions. ◆ Conclusions: Knowledge of the pathogenesis of peritoneal fibrosis has allowed independent researchers to design therapeutic strategies that abrogate excess matrix synthesis and deposition in cultured peritoneal cells and in animal models of experimental peritoneal fibrosis alike. Encouraging results have been obtained in those studies, but it remains to be determined whether the studied strategies can alleviate clinical disease. Future studies will enable us to establish specific molecules that can be targeted clinically to restrict the progressive deterioration of the peritoneal membrane as a biologic dialyzing organ.