Recent Concepts in the Molecular Biology of the Peritoneal Membrane – Implications for More Biocompatible Dialysis Solutions

Abstract

This paper reviews some important recent findings on the molecular biology of the peritoneal membrane. It attempts to correlate in vitro and in vivo experimental results with the possible clinical consequences. The most common functional alteration during long-term CAPD is increased peritoneal small-solute transport rate, resulting in impaired ultrafiltration and decreased dialysis efficiency. This contribution first discusses the most relevant advances in the biochemistry and molecular biology of the peritoneal membrane following peritonitis and as consequence of the continuous exposure to unphysiological dialysis fluids. In a second part the preliminary experimental and clinical experience with more biocompatible fluids is summarized. The most relevant structural and functional alterations of the membrane following repeated peritonitis is the consequence of the response of the peritoneum to infective organisms involving the inflammatory cytokines and the interaction between membrane resident cell populations: macrophages, mesothelial cells and fibroblasts. In this setting, human biopsy studies and animal experiments have identified an increase in the peritoneal-associated vasculature, which seems to be the primary cause of increased solute transport. The structural and functional alterations in the membrane in long-term peritoneal dialysis are thought to be the consequence of the toxicity of glucose, either directly or indirectly through the generation of glucose degradation products or the formation of advanced glycation end-products. In particular, an important role for vascular endothelial growth factor and nitric oxide as downstream mediators of the alterations has been suggested. Finally, the last part of this paper reviews the actual and future research aimed at an amelioration of the biocompatibility of the dialysis fluids. Replacing glucose by other osmotic agents, changing the sterilization process, replacing the lactate buffer by bicarbonate, blocking the formation of reactive carbonyl products and of the neoangiogenesis are the most promising changes to enhance the biocompatibility. Finally, gene therapy may in the future have an important contribution. Ex vivo gene therapy involves harvesting peritoneum samples to isolate mesothelial cells that will be genetically modified before re-implantation into the peritoneal cavity.

Association between Markers of Inflammation, Fibrosis and Hypervolemia in Peritoneal Dialysis Patients

“…Exposure of peritoneal tissues to high glucose levels may lead to inflammation and fibrosis through the action of advanced glycation end products [31, 32]. …”

Effect of Ligustrazine on rat peritoneal mesothelial cells treated with lipopolysaccharide

“…Peritoneal fibrosis and acute peritonitis are two main complications associated with PD, and these are associated with loss of mesothelial cells. 43 The protect effect of Ligustrazine can help to maintain peritoneal membrane function longer in patients undergoing CAPD, thus improve PD outcomes. However, further work is needed to explore the effects of Ligustrazine on peritoneal function in a proper animal model.…”

Role of Ultrafiltration in Peritoneal Dialysis: A Review

“…Uremia: Circulating factors like nitric oxide (NO), advanced glycation end products (AGEs), vascular endothelial growth factor (VEGF), and inflammatory cytokines [interleukin (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6] are all significantly increased in the uremic milieu. 13 The increase in effective peritoneal surface area is strongly related to VEGF and NO.…”