Preventing peritoneal dialysis-associated fibrosis by therapeutic blunting of peritoneal toll-like receptor activity

Raby, Anne-Catherine and Labeta, Mario 2018. Preventing peritoneal dialysis-associated fibrosis by therapeutic blunting of peritoneal toll-like receptor activity. Frontiers in Physiology 9 , 1692. 10.3389/fphys.2018.01692

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Abstract

Peritoneal dialysis (PD) is an essential daily life-saving treatment for end-stage renal failure. PD therapy is limited by peritoneal inflammation, which leads to peritoneal membrane failure as a result of progressive fibrosis. Peritoneal infections, with the concomitant acute inflammatory response and membrane fibrosis development, worsen PD patient outcomes. Patients who remain infection-free, however, also show evidence of inflammation-induced membrane damage and fibrosis, leading to PD cessation. In this case, uraemia, prolonged exposure to bio-incompatible PD solutions and surgical catheter insertion have been reported to induce sterile peritoneal inflammation and fibrosis as a result of cellular stress or tissue injury. Attempts to reduce inflammation (either infection-induced or sterile) and, thus, minimize fibrosis development in PD have been hampered because the immunological mechanisms underlying this PD-associated pathology remain to be fully defined. Toll-like receptors (TLRs) are central to mediating inflammatory responses by recognizing a wide variety of microorganisms and endogenous components released following cellular stress or generated as a consequence of extracellular matrix degradation during tissue injury. Given the close link between inflammation and fibrosis, recent investigations have evaluated the role that TLRs play in infection-induced and sterile peritoneal fibrosis development during PD. Here, we review the findings and discuss the potential of reducing peritoneal TLR activity by using a TLR inhibitor, soluble TLR2, as a therapeutic strategy to prevent PD-associated peritoneal fibrosis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Frontiers Media
ISSN:	1664-042X
Date of First Compliant Deposit:	27 November 2018
Date of Acceptance:	9 November 2018
Last Modified:	20 Oct 2019 18:22
URI:	http://orca-mwe.cf.ac.uk/id/eprint/117115

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