Matrix Metalloproteinases Cause Peritoneal Injury in Peritoneal Dialysis

Abstract

Long-term peritoneal dialysis (PD) leads to peritoneal injury with functional decline, such as ultrafiltration loss. Peritoneal injury is often accompanied by histological changes, such as peritoneal fibrosis and sclerosis. These complications involve evident diffuse fibrous thickening and/or edema of the peritoneum, and chronic inflammation (epithelial to mesenchymal transition of mesothelial cells as well as migration and proliferation of polynuclear leucocytes, macrophages, and mesenchymal cells in the peritoneum). At worst, peritoneal injury leads to encapsulating peritoneal sclerosis (EPS), a serious complication of PD [1-6]. At early stage of EPS (preEPS stage), peritoneal effluent with signs of inflammation is often observed [2]. At advanced stages of EPS, the small intestine adheres and is encapsulated within a collagen rich thick peritoneum to form a cocoon-like mass. As a result, EPS is associated with clinical symptoms, such as loss of appetite, nausea, vomiting, and emaciation due to malnutrition, as well as symptoms of intestinal obstruction that include abdominal pain, diarrhea, constipation, or lowered peristaltic bowel sounds. The incidence of EPS is not high: it occurs in about 0.4%–3.3% of patients who undergo PD. However, EPS has a high mortality rate, about half of the patients with EPS die [2-5]. The causes of functional disorders of the peritoneum are believed to be fibrosis, sclerosis, inflammation, angiogenesis, and vasculopathy. Peritoneal injury is probably caused by multiple factors, such as infection with bacteria or fungi resulting in peritonitis [2, 5, 6]; antiseptics [7-11]; exogenous materials like particulates and plasticizers [7]; and continuous exposure to nonphysiological PD solutions having high concentrations of glucose and glucose degradation products (GDPs), low pH, and high osmolarity [2, 12, 13]. Administration of corticosteroids, tamoxifen, immunosuppressive agents, and total parenteral nutrition are effective in the early stage of EPS development [2-4, 6]. However, for advanced EPS, in which bowel adhesions have formed, the only effective therapeutic method is surgical dissection of the encapsulated peritoneum; this must be performed by skilled surgeons using specialized techniques [2-5, 7]. It is important to monitor peritoneal injury, and develop methods for an early diagnosis of EPS. At present, major diagnostic methods for EPS include abdominal palpation (for identification of a mass) and finding clinical symptoms of bowel obstruction, like those found in the ileus [2]. However, these are not objective criteria and it is not rare that no typical symptoms are found even in advanced cases of EPS. Some physicians utilize diagnostic imaging methods for detection of EPS, such