Peritoneal dialysis serves as a critical treatment modality for end-stage renal disease. Extensive clinical practice has demonstrated that long-term exposure to high-glucose non-physiological peritoneal dialysis solutions can induce peritoneal injury, which is directly associated with a decline in ultrafiltration function and solute clearance capacity. This represents a significant cause of technical failure in dialysis and adverse clinical outcomes, such as peritonitis. Mesothelial cells and the glycocalyx on their surface, acting as the direct barrier between the peritoneum and the dialysis solution, play essential roles in regulating multiple pathophysiological processes, including fibrosis and inflammation, and are crucial for maintaining peritoneal function. This review provides a brief introduction to mesothelial cells and the glycocalyx, with a focus on elucidating the injury to the mesothelium and glycocalyx caused by high-glucose non-physiological peritoneal dialysis solutions, the associated injury mechanisms, and potential protective strategies. The aim is to offer insights for developing novel therapeutic approaches to preserve the structural and functional integrity of the peritoneum and extend the survival of patients undergoing peritoneal dialysis.
