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.
Creators: name: Lim, Wai H
name: Adams, Brigitte
name: Alexander, Stephen
name: Bouts, Antonia HM
name: Claas, Frans
name: Collins, Michael
name: Cornelissen, Elisabeth
name: Dunckley, Heather
name: De Jong, Huib
name: D'Orsogna, Lloyd
name: Francis, Anna
name: Heidt, Sebastiaan
name: Herman, Jean
name: Holdsworth, Rhonda
name: Kausman, Joshua
name: Khalid, Rabia
name: Kim, Jon Jin
name: Kim, Siah
name: Knops, Noël
name: Kosmoliaptsis, Vasilis
name: Kramer, Cynthia
name: Kuypers, Dirk
name: Larkins, Nicholas
name: Palmer, Suetonia C
name: Prestidge, Chanel
name: Prytula, Agnieszka
name: Sharma, Ankit
name: Shingde, Meena
name: Taverniti, Anne
name: Teixeira-Pinto, Armando
name: Trnka, Peter
name: Willis, Francis
name: Wong, Daniel
name: Wong, Germaine
Publisher: name: Apollo - University of Cambridge Repository
Year: 2021
Subjects: Study Protocol
Kidney transplant
Children
Adolescents
Parental donor
Immunological profile
Human leukocyte antigen
Antibody
Rejection
Allograft loss

description: 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 &gt; 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).