Membrane Biology During Peritoneal Dialysis

Peritoneal dialysis (PD) is a life-supporting renal replacement therapy used by 10-15% of patients with end-stage renal failure worldwide. The success of long-term PD depends entirely on the longevity and integrity of the peritoneal membrane. The peritoneum is covered by a mesothelial monolayer beneath which is a basement membrane and submesothelial layer that contains collagen, fibroblasts, adipose tissue, blood vessels and lymphatics. During PD, peritoneal cells are repeatedly exposed to a non-physiological hypertonic environment with high glucose content and low pH. Mesothelial cells (MCs) play an important role in regulating the inflammatory response in the peritoneal cavity: they produce pro-inflammatory cytokines and chemoattractants. By secreting these chemokines or cytokines, MCs contribute to the recruitment of leukocytes following the expression of adhesion molecules. Chronic changes in the peritoneum with fibrosis develop after years of peritoneal dialysis. The most marked changes are in cases of severe and recurrent peritonitis. Others have made similar observations that long-term exposure to peritoneal dialysis solutions appears to increase fibrosis and the probability of ultrafiltration failure. Encapsulating peritoneal sclerosis represents the most severe and fatal complication of membrane failure. Conventional peritoneal dialysis fluids (PDFs) make use of the osmotic gradient generated by glucose. Years of exposure to PDFs compounded with peritonitis result in the formation of an avascular layer of interstitial matrix and plasma proteins in the sub-mesothelial compact zone and an epithelial-to-mesenchymal transition (EMT) of mesothelial cells [1]. The fibrotic process in the peritoneal membrane is developed following acute and chronic release of inflammatory mediators related to PD. Independent extrinsic and intrinsic events (Table 1) contribute to chronic inflammation in patients on PD leading to complications including peritoneal membrane ultrafiltration failure, fluid overload, protein energy wasting and even atherosclerosis.