Agents that modulate peritoneal membrane structure and function

Extensive experience with chronic peritoneal dialysis has identified a series of functional and anatomical pathologic changes in the peritoneal membrane thought to be the result of repeated insults from bioincompatible solutions. Laboratory and clinical findings from recent investigations often conflict and are difficult to interpret due to variations in methodologies, animal models, study designs, and data analyses. The principal pathophysiologic mechanisms identified thus far are oxidative stress, inflammation, and their consequences. Many substances used to neutralize the action of these insults, prevent formation of toxic compounds, or directly alter solute and water transport to improve peritoneal membrane performance have been studied. We herein review the most promising of these substances or those that deserve attention because their use has contributed to better understanding of peritoneal pathophysiology. Most peritoneal solution additives have proved useless due to their toxicity and undesirable effects, ineffectiveness, or manufacturing limitations. A few substances deserve more attention, particularly those capable of restoring negatively charged membrane sites, those that somehow improve permselectivity, scavengers of oxidants, and advanced glycation end-product inhibitors and breakers. Recent publications on clinical experience with neutral pH, low glucose degradation product (GDP) peritoneal solutions, although few and preliminary, are most encouraging. The virtual elimination of GDPs in these novel solutions will probably preclude the need for GDP scavengers and inhibitors. Nonetheless, there is room for further significant improvement in solution biocompatibility and for compounds that may restore peritoneal function.