Peritoneal fibrosis intervention.
Peritoneal fibrosis (PF) is invariably observed in patients undergoing long-term peritoneal dialysis (PD). The condition is thought to occur in response to a variety of insults, including bioincompatible dialysates (acidic solution, high glucose, glucose degradation products, or a combination), peritonitis, uremia, and chronic inflammation. Recently, the pathophysiologic mechanisms that contribute to the fibrosing process have been intensively studied. Transforming growth factor-beta has been shown to be a key mediator of PF. Loss of the mesothelial cell layer has been identified in several studies and shown to correlate with submesothelial thickening and vasculopathy. An association has also been identified between increased submesothelial thickness in the peritoneal membrane and increased solute transport, suggesting a relationship between PF and loss of ultrafiltration capacity. Thus, to maintain long-term PD and improve quality of life for patients, it is important to develop interventions for prevention and treatment of PF. Several strategies for peritoneal fibrosis intervention have been reported, including developing biocompatible dialysate, targeting mediators responsible for inflammation and fibrosis, and reconstituting the peritoneum using mesothelial or bone marrow-derived cells. Recent experimental trials in animal models and clinical studies are presented in this review.
Kaneko
Kayo
K
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Hamada
Chieko
C
Tomino
Yasuhiko
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001672:Biocompatible Materials; D015314:Dialysis Solutions / Q000737:chemistry; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000517:prevention & control*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology*; D011347:Procollagen / Q000097:blood; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000097:blood; D062367:ortho-Aminobenzoates / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001672:Biocompatible Materials; D015314:Dialysis Solutions; D018836:Inflammation Mediators; D010446:Peptide Fragments; D011347:Procollagen; D016212:Transforming Growth Factor beta; D062367:ortho-Aminobenzoates; C041876:procollagen Type III-N-terminal peptide; D006820:Hyaluronic Acid; C012293:tranilast