Peritoneal mesothelial cell biology in peritoneal dialysis

Abstract

SUMMARY: Progressive peritoneal membrane hyperpermeability, ultrafiltration failure, and peritoneal fibrosis have been observed in long‐term peritoneal dialysis (PD) patients, and these alterations in peritoneal structure and function may be responsible for the poor technique survival in PD. While frequent and/or severe peritonitis can result in alterations of the peritoneum, continuous exposure of the peritoneum to PD solutions may also adversely affect peritoneal structure and function. Peritoneal mesothelial cells (PMC) are directly and continuously exposed to unphysiological components of PD solution. Low pH, lactate, hyperosmolality, and glucose degradation products (GDP) reduce PMC viability and proliferation. High glucose, GDP, and advanced glycation end products (AGE) upregulate vascular endothelial growth factor (VEGF), monocyte chemoattractant protein (MCP)‐1, transforming growth factor (TGF)‐β1, plasminogen activator inhibitor (PAI)‐1, and extracellular matrix protein expression by PMC, and may thus lead to peritoneal hyperpermeability, ultrafiltration failure, and peritoneal fibrosis, as observed in long‐term PD. Activation of diacylglycerol (DAG)‐protein kinase C (PKC) and generation of reactive oxygen species (ROS) are important upstream signalling events in high glucose‐induced PMC activation. Thus, strategies to inhibit high glucose‐induced PKC activation and ROS generation and the use of new PD solutions with non‐glucose osmotic agents, pH neutral solutions, or solutions containing low GDP may allow better preservation of the structural and functional integrity of the peritoneal membrane during long‐term PD.