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

Lim, W.H.; Adams, B.; Alexander, S.; Bouts, A.H.M.; Claas, F.; Collins, M.; ... ; Wong, G. (2021)

Article / Letter to editor

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 <= 18years 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, biopsyproven 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.

• Kidney transplant
• Children
• Adolescents
• Parental donor
• Immunological profile
• Human leukocyte antigen
• Antibody
• Rejection
• Allograft loss

• All authors: Lim, W.H.; Adams, B.; Alexander, S.; Bouts, A.H.M.; Claas, F.; Collins, M.; Cornelissen, E.; Dunckley, H.; Jong, H. de; D'Orsogna, L.; Francis, A.; Heidt, S.; Herman, J.; Holdsworth, R.; Kausman, J.; Khalid, R.; Kim, J.J.; Kim, S.; Knops, N.; Kosmoliaptsis, V.; Kramer, C.; Kuypers, D.; Larkins, N.; Palmer, S.C.; Prestidge, C.; Prytula, A.; Sharma, A.; Shingde, M.; Taverniti, A.; Teixeira-Pinto, A.; Trnka, P.; Willis, F.; Wong, D.; Wong, G.
• Date: 2021-12-19
• Journal: BMC Nephrology
• Volume: 22
• Issue: 1
• DOI: doi:10.1186/s12882-021-02619-0
• Link: https://bmcnephrol.biomedcentral.com/track/pdf/10.1186/s12882-021-02619-0