What Can We Do to Preserve the Peritoneum?

Abstract

Long-term peritoneal dialysis may lead to peritoneal membrane failure. Loss of ultrafiltration is the most important clinical abnormality. Loss of ultrafiltration is associated with an increased number of peritoneal blood vessels, with fibrotic alterations, and with loss of mesothelium. Continuous exposure to bioincompatible dialysis solutions is likely to be important in the pathogenesis of these alterations. This article reviews the toxicity of various constituents of dialysate, current assessments of interventions, and the results of interventions aimed at preserving the peritoneum. Glucose, possibly in combination with lactate, and glucose degradation products (GDPs) are likely to be the most toxic constituents of dialysate. Diabetiform peritoneal neoangiogenesis is likely to be mediated by vascular endothelial growth factor (VEGF). Release of VEGF might be influenced by glucose-induced cellular pseudohypoxia, which is likely to be increased by exposure to lactate. Glucose and GDPs are both toxic to peritoneal cells. Glucose degradation products induce the formation of advanced glycosylation end-products at a much faster rate than does glucose itself, but the relative importance of GDPs and glucose in clinical PD has not been clarified. The effects of interventions should first be assessed in long-term animal models, followed by clinical studies on peritoneal transport and on effluent markers that may reflect the status of the peritoneum. Possible interventions aim at reducing peritoneal exposure to glucose, GDPs, and lactate. Techniques include peritoneal resting, replacing some glucose-based exchanges with amino acid-based and icodextrin-based dialysate, using bicarbonate as a buffer, and administering solutions that have a low GDP content. Exposure to various dialysis solutions with a reduced GDP content has resulted in an increase in the effluent concentration of the mesothelial cell marker CA125, irrespective of the buffer used. Experimental studies in a long-term peritoneal exposure model in rats showed that the combination of a reduction in the concentration of lactate and replacement of lactate with pyruvate resulted in a reduction of the number of peritoneal blood vessels. Results of drug therapy have been studied in various animal models. Their use in patients is still experimental. Strategies to preserve the peritoneum aim at reducing membrane exposure to bioincompatible solutions. Currently available dialysis fluids that are more biocompatible are likely to have some beneficial effects. Further research on the development of dialysis solutions that use combinations of osmotic agents and alternative buffers is necessary.