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©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. Oct 27, 2019; 8(6): 95-108
Published online Oct 27, 2019. doi: 10.5527/wjn.v8.i6.95
Complement activation and long-term graft function in ABO-incompatible kidney transplantation
Marit S van Sandwijk, Astrid Klooster, Ineke JM ten Berge, Arjan Diepstra, Sandrine Florquin, Joris J Hoelbeek, Frederike J Bemelman, Jan-Stephan Sanders
Marit S van Sandwijk, Ineke JM ten Berge, Frederike J Bemelman, Department of Nephrology, Amsterdam University Medical Centers, Amsterdam NL-1105 AZ, Netherlands
Marit S van Sandwijk, Dianet Dialysis Center, Amsterdam NL-1105 AZ, Netherlands
Astrid Klooster, Arjan Diepstra, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen NL-9700 RB, Netherlands
Astrid Klooster, Department of Pathology, Pathology Friesland, Leeuwarden NL-8917 EN, Netherlands
Sandrine Florquin, Joris J Hoelbeek, Department of Pathology, Amsterdam University Medical Centers, Amsterdam NL-1105 AZ, Netherlands
Jan-Stephan Sanders, Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen NL-9700 RB, Netherlands
Author contributions: van Sandwijk MS, Klooster A, Bemelman FJ, and Sanders JS designed the study; van Sandwijk MS and Klooster A collected and analyzed the clinical data; Diepstra A, Florquin S, and Hoelbeek JJ collected and analyzed the biopsy data; van Sandwijk MS wrote the first draft of the article; all other authors reviewed the draft, provided expertise for revisions, and approved the final version of the manuscript.
Institutional review board statement: In this study, anonymized patient information was retrospectively obtained and analyzed. This information was available from the Dutch Organ Transplantation Registry. All subjects consented to being included in this Registry at the time of transplantation. All subjects of this study were treated according to standard clinical practice, and their treatment or clinical outcomes were not in any way affected by their retrospective inclusion in this study. As the subjects of this study were not subjected to procedures nor were required to follow rules of behaviour, Institutional Review Board approval was not required according to Dutch law.
Informed consent statement: Patient consent was not obtained but the presented data are anonymized and risk of identification is low.
Conflict-of-interest statement: All authors declare no potential conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at m.s.vansandwijk@amsterdamumc.nl.
STROBE statement: The authors have read the STROBE Statement – checklist of items, and the manuscript was prepared and revised according to the STROBE Statement – checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Marit S van Sandwijk, MD, Staff Physician, Internist-Nephrologist, Department of Nephrology, Amsterdam University Medical Centers, location AMC, Meibergdreef 9, Amsterdam NL-1105 AZ, Netherlands. m.s.vansandwijk@amsterdamumc.nl
Telephone: +31-20-5662596
Received: May 22, 2019
Peer-review started: May 23, 2019
First decision: August 1, 2019
Revised: August 29, 2019
Accepted: October 18, 2019
Article in press: October 18, 2019
Published online: October 27, 2019
ARTICLE HIGHLIGHTS
Research background
Short-term graft and patient survival in ABO-incompatible kidney transplantation are equivalent to ABO-compatible kidney transplantation, but in ABO-incompatible kidney transplantation, ongoing activation of complement by anti-ABO antibodies might adversely affect long-term graft function.
Research motivation
We aimed to investigate whether ongoing complement activation in ABO-incompatible kidney transplantation could explain why long-term graft function is impaired in ABO-incompatible kidney transplantation compared to ABO-compatible kidney transplantation.
Research objectives
To measure long-term graft function in all ABO-incompatible kidney transplantation recipients at the Academic Medical Center Amsterdam and the University Medical Center Groningen, compare this to long-term graft function in matched ABO-compatible kidney transplantation recipients and relate this to various markers of complement activation.
Research methods
We used linear mixed models to estimate long-term graft function decline in both ABO-incompatible and matched ABO-compatible kidney transplantation recipients. Matching criteria were age, sex, and transplantation date. AB O-incompatible kidney biopsies were stained for various markers of complement activation.
Research results
The slope of kidney function during five-year follow-up was not significantly different between ABO-incompatible and ABO-compatible kidney transplantation, but ABO-incompatible kidney transplant recipients did have a lower function at three months after transplantation due to a high rate of early mostly T-cell mediated rejection. Rejection and C5b-9 activation were positively correlated.
Research conclusions
Ongoing complement activation adversely affects long-term graft function in ABO-incompatible kidney transplantation. We hypothesize that this may be due to concurrent C5a formation, which functions as a costimulatory signal for T-cell activation.
Research perspectives
Further studies are needed to confirm whether ongoing C5a formation is responsible for T-cell mediated rejection in ABO-incompatible kidney transplantation.
