Molecular mechanisms modifying the peritoneal membrane exposed to peritoneal dialysis.
Over time, a significant proportion of patients an peritoneal dialysis (PD) develop an increased permeability for small solutes, which induces a faster absorption of glucose, and ultrafiltration failure by early dissipation of the osmotic gradient. Vascular proliferation and vasodilatation of preexisting vessels might represent the structural basis for increased effective peritoneal surface area encountered in these PD patients. Animal models have shown that local release of growth factors and nitric oxide in the peritoneal membrane (PM) may lead to the development of areas of neovascularization and/or submesothelial fibrosis. Long-term exposure to conventional, glucose-based dialysis fluids plays a central role in the pathogenesis of these structural modifications. Glucose degradation products and reactive carbonyl species, which are present both in glucose-based dialysates and uremic plasma, accelerate the formation of the advanced glycation end products in the PM, which may in turn initiate a range of cellular responses including stimulation of monocytes, secretion of inflammatory cytokines, proliferation of vascular smooth muscle cells, stimulation of growth factors, and secretion of matrix proteins. The changes in the PM may also be potentiated by uremia and hyperglycemia per se. These new insights into the molecular mechanisms operating in the PM have provided rationale for novel therapeutic strategies including the development of glucose-free PD solutions and two-chamber bags.
Gillerot
G
G
Division of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium.
Devuyst
O
O
D000818:Animals; D002199:Capillary Permeability; D015314:Dialysis Solutions / Q000494:pharmacology; D005355:Fibrosis; D006801:Humans; D009389:Neovascularization, Pathologic; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D015314:Dialysis Solutions