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Front. Physiol. | doi: 10.3389/fphys.2018.01692

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

 Mario O. Labéta1* and Anne C. Raby1
  • 1The Wales Kidney Research Unit, Division of Infection & Immunity,, School of Medicine, Cardiff University, United Kingdom

Peritoneal dialysis (PD) is an essential daily life-saving treatment for end-stage renal failure. A major factor limiting PD therapy remains 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, minimise 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 recognising a wide variety of microorganisms as well as 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 therapeutic potential of blunting peritoneal TLR activity to prevent PD-associated peritoneal fibrosis by using a TLR modulator, the soluble form of TLR2.

Keywords: peritoneal dialysis (PD), Inflammation, Peritoneal Fibrosis, Toll-Like Receptors, Soluble Toll-like receptor 2 (sTLR2)

Received: 10 Aug 2018; Accepted: 09 Nov 2018.

Edited by:

Janusz Witowski, Poznan University of Medical Sciences, Poland

Reviewed by:

Bruno Vogt, University of Bern, Switzerland
Christoph Aufricht, Medical University of Vienna, Austria  

Copyright: © 2018 Labéta and Raby. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Mario O. Labéta, School of Medicine, Cardiff University, The Wales Kidney Research Unit, Division of Infection & Immunity,, Cardiff, United Kingdom, Labeta@cardiff.ac.uk