What is Encapsulating Peritoneal Sclerosis (EPS)?

Encapsulating peritoneal sclerosis (EPS), also known as abdominal cocoon syndrome, is a rare and serious complication of long-term peritoneal dialysis (PD), a type of renal replacement therapy used to treat end-stage kidney disease. EPS is characterized by the progressive thickening and fibrosis of the peritoneal membrane, the lining of the abdominal cavity, leading to the formation of a dense fibrous cocoon-like structure around the small bowel and other intra-abdominal organs.


The exact cause of encapsulating peritoneal sclerosis is not fully understood, but it is believed to result from chronic inflammation and fibrosis of the peritoneal membrane, which may be triggered by prolonged exposure to PD solutions, repeated episodes of peritonitis (inflammation of the peritoneum), and other factors. Individuals with a history of long-term peritoneal dialysis, typically over several years, are at increased risk of developing EPS.


What is the relationship between EPS and oxidative stress?

The relationship between encapsulating peritoneal sclerosis (EPS) and oxidative stress is not fully understood and remains an area of ongoing research. However, several mechanisms may link oxidative stress to the pathogenesis and progression of EPS:


  • Chronic Inflammation: EPS is characterized by chronic inflammation and fibrosis of the peritoneal membrane, which may be triggered by repeated episodes of peritonitis, prolonged exposure to peritoneal dialysis (PD) solutions, and other factors. Inflammatory processes involve the activation of immune cells and the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species (ROS). ROS generated during inflammation contribute to oxidative stress and tissue damage in the peritoneal membrane, promoting fibrosis and the formation of an encapsulating cocoon-like structure.


  • Oxidative Damage to Peritoneal Cells: ROS can directly damage peritoneal mesothelial cells, the cells that line the peritoneal cavity. Oxidative stress-induced damage to mesothelial cells disrupts their barrier function, impairs the integrity of the peritoneal membrane, and promotes fibroblast activation and collagen deposition. These changes contribute to the thickening and fibrosis of the peritoneal membrane characteristic of EPS.


  • Mitochondrial Dysfunction: Oxidative stress can impair mitochondrial function in peritoneal cells, leading to mitochondrial dysfunction and increased ROS production. Mitochondrial dysfunction contributes to cellular oxidative damage, inflammation, and apoptosis (programmed cell death) in the peritoneal membrane, exacerbating fibrosis and tissue remodeling in EPS.


  • Protein Glycation and Advanced Glycation End Products (AGEs): Chronic exposure to glucose-based PD solutions can lead to the accumulation of advanced glycation end products (AGEs) in the peritoneal membrane. AGEs are formed through non-enzymatic reactions between glucose and proteins and contribute to oxidative stress, inflammation, and tissue fibrosis. AGEs can induce oxidative damage to cellular components, activate pro-fibrotic signaling pathways, and promote extracellular matrix deposition in the peritoneal membrane, exacerbating fibrosis and EPS progression.


  • Impaired Antioxidant Defenses: Oxidative stress in EPS may be exacerbated by impaired antioxidant defenses in the peritoneal cavity. Chronic exposure to PD solutions and inflammation can deplete antioxidants such as glutathione and superoxide dismutase, reducing the ability of peritoneal cells to neutralize ROS and protect against oxidative damage. Impaired antioxidant defenses contribute to oxidative stress-mediated tissue injury and fibrosis in EPS.


Overall, oxidative stress appears to play a significant role in the pathogenesis and progression of encapsulating peritoneal sclerosis through its effects on inflammation, cellular damage, mitochondrial dysfunction, and fibrosis in the peritoneal membrane.