Improve in-depth immunological risk assessment to optimize genetic-compatibility and clinical outcomes in child and adolescent recipients of parental donor kidney transplants: protocol for the INCEPTION study
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Published:2021-12
Issue:1
Volume:22
Page:
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ISSN:1471-2369
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Container-title:BMC Nephrology
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language:en
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Short-container-title:BMC Nephrol
Author:
Lim Wai H.ORCID, Adams Brigitte, Alexander Stephen, Bouts Antonia H. M., Claas Frans, Collins Michael, Cornelissen Elisabeth, Dunckley Heather, de Jong Huib, D’Orsogna Lloyd, Francis Anna, Heidt Sebastiaan, Herman Jean, Holdsworth Rhonda, Kausman Joshua, Khalid Rabia, Kim Jon Jin, Kim Siah, Knops Noël, Kosmoliaptsis Vasilis, Kramer Cynthia, Kuypers Dirk, Larkins Nicholas, Palmer Suetonia C., Prestidge Chanel, Prytula Agnieszka, Sharma Ankit, Shingde Meena, Taverniti Anne, Teixeira-Pinto Armando, Trnka Peter, Willis Francis, Wong Daniel, Wong Germaine
Abstract
Abstract
Background
Parental donor kidney transplantation is the most common treatment option for children and adolescents with kidney failure. Emerging data from observational studies have reported improved short- and medium-term allograft outcomes in recipients of paternal compared to maternal donors. The INCEPTION study aims to identify potential differences in immunological compatibility between maternal and paternal donor kidneys and ascertain how this affects kidney allograft outcomes in children and adolescents with kidney failure.
Methods
This longitudinal observational study will recruit kidney transplant recipients aged ≤18 years who have received a parental donor kidney transplant across 4 countries (Australia, New Zealand, United Kingdom and the Netherlands) between 1990 and 2020. High resolution human leukocyte antigen (HLA) typing of both recipients and corresponding parental donors will be undertaken, to provide an in-depth assessment of immunological compatibility. The primary outcome is a composite of de novo donor-specific anti-HLA antibody (DSA), biopsy-proven acute rejection or allograft loss up to 60-months post-transplantation. Secondary outcomes are de novo DSA, biopsy-proven acute rejection, acute or chronic antibody mediated rejection or Chronic Allograft Damage Index (CADI) score of > 1 on allograft biopsy post-transplant, allograft function, proteinuria and allograft loss. Using principal component analysis and Cox proportional hazards regression modelling, we will determine the associations between defined sets of immunological and clinical parameters that may identify risk stratification for the primary and secondary outcome measures among young people accepting a parental donor kidney for transplantation. This study design will allow us to specifically investigate the relative importance of accepting a maternal compared to paternal donor, for families deciding on the best option for donation.
Discussion
The INCEPTION study findings will explore potentially differential immunological risks of maternal and paternal donor kidneys for transplantation among children and adolescents. Our study will provide the evidence base underpinning the selection of parental donor in order to achieve the best projected long-term kidney transplant and overall health outcomes for children and adolescents, a recognized vulnerable population.
Trial registration
The INCEPTION study has been registered with the Australian New Zealand Clinical Trials Registry, with the trial registration number of ACTRN12620000911998 (14th September 2020).
Publisher
Springer Science and Business Media LLC
Reference51 articles.
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