TY - JOUR
T1 - Improve in-depth immunological risk assessment to optimize genetic-compatibility and clinical outcomes in child and adolescent recipients of parental donor kidney transplants
T2 - protocol for the INCEPTION study
AU - Lim, Wai H.
AU - Adams, Brigitte
AU - Alexander, Stephen
AU - Bouts, Antonia H.M.
AU - Claas, Frans
AU - Collins, Michael
AU - Cornelissen, Elisabeth
AU - Dunckley, Heather
AU - de Jong, Huib
AU - D’Orsogna, Lloyd
AU - Francis, Anna
AU - Heidt, Sebastiaan
AU - Herman, Jean
AU - Holdsworth, Rhonda
AU - Kausman, Joshua
AU - Khalid, Rabia
AU - Kim, Jon Jin
AU - Kim, Siah
AU - Knops, Noël
AU - Kosmoliaptsis, Vasilis
AU - Kramer, Cynthia
AU - Kuypers, Dirk
AU - Larkins, Nicholas
AU - Palmer, Suetonia C.
AU - Prestidge, Chanel
AU - Prytula, Agnieszka
AU - Sharma, Ankit
AU - Shingde, Meena
AU - Taverniti, Anne
AU - Teixeira-Pinto, Armando
AU - Trnka, Peter
AU - Willis, Francis
AU - Wong, Daniel
AU - Wong, Germaine
N1 - Funding Information:
Funding for the INCEPTION study is provided by the National Health and Medical Research Council (NHMRC) Ideas Grant (Application ID: APP1184595, funding duration 2020-2023), the Department of Health Western Australia and the Telethon-Perth Children’s Hospital Research Fund (funding duration 2017-2020) and Starship Foundation Clinical Research Grant (Auckland, New Zealand). All funding were subjected to vigorous full external peer-review processes.
Funding Information:
The INCEPTION study is a longitudinal observational study that will recruit pediatric and adolescent transplant recipients aged ≤18 years who have received parental donor kidneys between January 1990 and December 2020 (Fig. ). Corresponding parental donors will also be recruited for inclusion in the study. Adult kidney transplant recipients of parental donor kidneys aged > 18 years at time of transplantation or recipients of deceased donor kidney transplants will be excluded. Funding for the INCEPTION study is provided by the National Health and Medical Research Council (NHMRC) Ideas Grant (Application ID: APP1184595, funding duration 2020-2023), the Department of Health Western Australia and the Telethon-Perth Children’s Hospital Research Fund (funding duration 2017-2020) and Starship Foundation Clinical Research Grant (Auckland, New Zealand). The reporting and conduct of the study will adhere to The Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines [].
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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).
AB - 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).
KW - Adolescents
KW - Allograft loss
KW - Antibody
KW - Children
KW - Human leukocyte antigen
KW - Immunological profile
KW - Kidney transplant
KW - Parental donor
KW - Rejection
UR - http://www.scopus.com/inward/record.url?scp=85121458672&partnerID=8YFLogxK
U2 - 10.1186/s12882-021-02619-0
DO - 10.1186/s12882-021-02619-0
M3 - Article
C2 - 34923958
AN - SCOPUS:85121458672
SN - 1471-2369
VL - 22
JO - BMC Nephrology
JF - BMC Nephrology
IS - 1
M1 - 416
ER -
