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
Year: 2021
Type: article
Study design: Study Protocol
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).
Source: BMC Nephrology
Authors: Wai H. Lim, Brigitte Adams, Stephen Alexander, Antonia H. M. Bouts, Frans Claas, Michael Collins, Elisabeth Cornelissen, Heather Dunckley, Huib de Jong, Lloyd D’Orsogna, Anna Francis, Sebastiaan Heidt, Jean Herman, Rhonda Holdsworth, Joshua Kausman, Rabia Khalid, Jon Jin Kim, Siah Kim, Noël Knops, Vasilis Kosmoliaptsis, Cynthia Kramer, Dirk Kuypers, Nicholas Larkins, Suetonia C. Palmer, Chanel Prestidge, Agnieszka Prytula, Ankit Sharma, Meena Shingde, Anne Taverniti, Armando Teixeira-Pinto, Peter Trnka, Francis Willis, Daniel Wong, Germaine Wong
Institutions: The University of Western Australia, Sir Charles Gairdner Hospital, Queen Fabiola Children's University Hospital, The University of Sydney, Children's Hospital at Westmead, Westmead Hospital, Emma Kinderziekenhuis, Amsterdam University Medical Centers, Leiden University, Leiden University Medical Center, University of Auckland, Auckland City Hospital, Auckland District Health Board, Radboud University Nijmegen, Radboud University Medical Center, Amalia Kinderziekenhuis, Erasmus MC, Fiona Stanley Hospital, The University of Queensland, Children's Health Queensland Hospital and Health Service, Universitair Ziekenhuis Leuven, Australian Red Cross Lifeblood, Royal Children's Hospital, The University of Melbourne, Murdoch Children's Research Institute, Guy's Hospital, Nottingham University Hospitals NHS Trust, Great Ormond Street Hospital, Great Ormond Street Hospital for Children NHS Foundation Trust, Medical Research Council, KU Leuven, University of Cambridge, National Institute for Health and Care Research, Addenbrooke's Hospital, NIHR Cambridge Biomedical Research Centre, Princess Margaret Hospital for Children, Perth Children's Hospital, University of Otago, Starship Children's Health, Ghent University Hospital, NSW Health Pathology, The University of Notre Dame Australia, Queen Elizabeth II Medical Centre
Language: English
Subfield: Transplantation
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,390
Awards: G309794119, G3728803030, Computational assessment of Human Leukocyte Antigen immunogenicity to improve donor-recipient histocompatibility and inform allocation policy in kidney transplantation and beyond, The assessment of novel immunological risk profile to establish the most suitable parental donor for kidney transplantation: “Best-Parent” study (ELIMINATE)
OpenAlex ID: W4200100712