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PERSPECTIVE article

Front. Nephrol.
Sec. Blood Purification
Volume 4 - 2024 | doi: 10.3389/fneph.2024.1455321

The Janus-Faced Nature of Complement in Hemodialysis: Interplay between Complement, Inflammation, and Bioincompatibility Unveiling a Self-Amplifying Loop Contributing to Organ Damage

Provisionally accepted
Bernard Canaud Bernard Canaud 1Peter Stenvinkel Peter Stenvinkel 2Anna R. Scheiwe Anna R. Scheiwe 3*Sonja Steppan Sonja Steppan 3Sudhir Bowry Sudhir Bowry 4Giuseppe Castellano Giuseppe Castellano 5
  • 1 Université de Montpellier, Montpellier, Languedoc-Roussillon, France
  • 2 Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet (KI), Huddinge, Stockholm, Sweden
  • 3 Other, Bad Homburg, Germany
  • 4 Other, Bad Nauheim, Germany
  • 5 Center for HUS Prevention, Control, and Management at the Nephrology and Dialysis Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

The final, formatted version of the article will be published soon.

    In hemodialysis (HD), complement activation, bioincompatibility, and inflammation are intricately intertwined. In the 1970s, as HD became a routine therapy, the observation of complement pathway activation and transient leukopenia by cellulosic dialysis membranes triggered the bioincompatibility debate and its clinical relevance. Extensive deliberations have covered definitions, assessment markers, scope, and long-term clinical consequences of membrane-dependent bioincompatibility reactions. While complement pathways' interplay with coagulation and inflammation has been delineated, HD's focus has primarily been on developing more biocompatible membranes using advanced technologies. Recent advances and understanding of the current HD delivery mode (4-hour sessions, thrice weekly) suggest that factors beyond membrane characteristics play a significant role, and a more complex, multifactorial picture of bioincompatibility is emerging. Chronic activation of the complement system and persistent low-grade "uremic inflammation" in chronic kidney disease (CKD) and HD lead to premature inflammaging of the kidney, resembling aging in the general population. Cellular senescence, modulated by complement activation and the uremic milieu, contributes to chronic inflammaging. Additionally, the formation of neutrophil extracellular traps (NETs, process of NETosis) during HD and their biological activity in the interdialytic period can lead to dialysis-induced systemic stress. Thus, complement-inflammation manifestations in HD therapies extend beyond traditional membrane-related bioincompatibility consequences. Recent scientific knowledge is Word count: reshaping strategies to mitigate detrimental consequences of bioincompatibility, both technologically and in HD therapy delivery modes, to improve dialysis patient outcomes.

    Keywords: Inflammation1, complement2, Biocompatibility3, dialysis4, technology5, Clinical impact6, Chronic kidney disease7

    Received: 26 Jun 2024; Accepted: 31 Oct 2024.

    Copyright: © 2024 Canaud, Stenvinkel, Scheiwe, Steppan, Bowry and Castellano. 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) or licensor 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: Anna R. Scheiwe, Other, Bad Homburg, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.