Pathogenesis and treatment of peritoneal membrane failure.
Peritoneal dialysis (PD) is a viable treatment option for end stage renal disease (ESRD) patients worldwide. PD may provide a survival advantages over hemodialysis (HD) in the early years of treatment. However, the benefits of PD are short-lived, as peritoneal membrane failure ensues in many patients, owing mainly to structural and functional changes in the peritoneal membrane from the use of conventional bio-incompatible PD solutions, which are hyperosmolar, acidic, have lactate buffer and contain high concentrations of glucose and glucose degradation products (GDPs). Current data suggest that chronic exposure of the peritoneum to contemporary PD fluids provokes activation of various inflammatory, fibrogenic and angiogenic cytokines, interplay of which leads to progressive peritoneal fibrosis, vasculopathy and neoangiogenesis. There is emerging evidence that peritoneal vascular changes are mainly responsible for increased solute transport and ultrafiltration failure in long-term PD. However, the precise pathophysiologic mechanisms initiating and propagating peritoneal fibrosis and angiogenesis remain elusive. The protection of the peritoneal membrane from long-term toxic and metabolic effects of high GDP-containing, conventional, glucose-based solutions is a prime objective to improve PD outcome. Recent development of new, more biocompatible, PD solutions should help to preserve peritoneal membrane function, promote ultrafiltration, improve nutritional status and, hopefully, preserve peritoneal membrane and improve overall PD outcomes. Elucidation of molecular mechanisms involved in the cellular responses leading to peritoneal fibrosis and angiogenesis spurs new therapeutic strategies that might protect the peritoneal membrane against the consequences of longstanding PD.
Saxena
Ramesh
R
Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8856, USA. Ramesh.saxena@utsouthwestern.edu
D002648:Child; D015314:Dialysis Solutions / Q000592:standards*; D004868:Equipment Failure; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008567:Membranes, Artificial; D010530:Peritoneal Dialysis / Q000295:instrumentation*; D012307:Risk Factors; D013997:Time Factors
D015314:Dialysis Solutions; D008567:Membranes, Artificial