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

BMC Nephrology

Anne Taverniti¹  Ankit Sharma²  Sebastiaan Heidt³  Cynthia Kramer³  Frans Claas³  Dirk Kuypers⁴  Joshua Kausman⁵  Siah Kim⁶  Stephen Alexander⁷  Jon Jin Kim⁸  Agnieszka Prytula⁹  Jean Herman^1,10  Noël Knops^1,11  Antonia H. M. Bouts^1,12  Brigitte Adams^1,13  Elisabeth Cornelissen^1,14  Michael Collins^1,15  Wai H. Lim^1,16  Vasilis Kosmoliaptsis^1,17  Huib de Jong^1,18  Lloyd D’Orsogna^1,19  Daniel Wong^2,20  Nicholas Larkins^2,21  Francis Willis^2,22  Meena Shingde^2,23  Heather Dunckley^2,24  Anna Francis^2,25  Peter Trnka^2,25  Chanel Prestidge^2,26  Armando Teixeira-Pinto^2,27  Rabia Khalid^2,28  Germaine Wong^2,29  Suetonia C. Palmer^3,30  Rhonda Holdsworth^3,31 

[1] Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, Sydney, Australia;Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, Sydney, Australia;Department of Renal Medicine, Westmead Hospital, Sydney, Australia;Department of Immunology, Leiden University Medical Centre, Leiden, The Netherlands;Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium;Department of Microbiology and Immunology, KU Leuven, University of Leuven, Leuven, Belgium;Department of Nephrology, Royal Children’s Hospital Melbourne, Parkville, Victoria, Australia;Murdoch Children’s Research Institute, Melbourne, Victoria, Australia;University of Melbourne, Melbourne, Victoria, Australia;Department of Nephrology, Westmead Children’s Hospital, Sydney, Australia;Department of Nephrology, Westmead Children’s Hospital, Sydney, Australia;Faculty of Medicine and Health, University of Sydney, Sydney, Australia;Department of Paediatric Nephrology, Nottingham University Hospital, Nottingham, UK;Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, WC1N 3JH, London, UK;MRC Centre for Transplantation, Guy’s Hospital, London, UK;Department of Pediatric Nephrology and Rheumatology, Ghent University Hospital, Ghent, Belgium;Department of Pediatric Nephrology and Solid Organ Transplantation, University Hospitals Leuven, Leuven, Belgium;Department of Pediatric Nephrology and Solid Organ Transplantation, University Hospitals Leuven, Leuven, Belgium;Department of Development and Regeneration (Woman and Child), KU Leuven, Leuven, Belgium;Department of Pediatric Nephrology, Emma Children’s Hospital, Amsterdam University Medical Center, Amsterdam, The Netherlands;Department of Pediatric Nephrology, Hôpital Universitaire des Enfants-Reine Fabiola, Brussels, Belgium;Department of Pediatric Nephrology, Radboud University Medical Center, Amalia Children’s Hospital, Nijmegen, The Netherlands;Department of Renal Medicine, Auckland District Health Board, Auckland City Hospital, Auckland, New Zealand;Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand;Department of Renal Medicine, Sir Charles Gairdner Hospital, 6009, Perth, Western Australia, Australia;Medical School, University of Western Australia, Perth, Australia;Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge, UK;UK and NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, University of Cambridge, Hills Road, Cambridge, UK;NIHR Cambridge Biomedical Research Centre, Hills Road, Cambridge, UK;Erasmus Medical Center, Rotterdam, The Netherlands;Faculty of Health and Medical Sciences, Pathology & Laboratory Medicine, University of Western Australia, Perth, Australia;Department of Clinical Immunology, Fiona Stanley Hospital, Perth, Australia;National Pancreas Unit, Westmead Hospital, Sydney, Australia;Medical School, University of Western Australia, Perth, Australia;Anatomical Pathology, PathWest, QEII Medical Centre, Perth, Australia;Medical School, University of Western Australia, Perth, Australia;Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, Sydney, Australia;Department of Nephrology, Perth Children’s Hospital, Perth, Australia;Medical School, University of Western Australia, Perth, Australia;Department of Nephrology, Perth Children’s Hospital, Perth, Australia;School of Medicine, University of Notre Dame (Fremantle), Perth, Australia;NSW Health Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, Sydney, Australia;New Zealand Transplantation and Immunogenetics Laboratory, New Zealand Blood Service, Auckland, New Zealand;School of Medicine, University of Queensland, Brisbane, Queensland, Australia;Child and Adolescent Renal Service, Children’s Health Queensland, Brisbane, Queensland, Australia;Starship Children’s Hospital, Auckland Health Board, Auckland, New Zealand;Sydney School of Public Health, The University of Sydney, Sydney, Australia;Sydney School of Public Health, The University of Sydney, Sydney, Australia;Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, Sydney, Australia;Sydney School of Public Health, The University of Sydney, Sydney, Australia;Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, Sydney, Australia;Department of Renal Medicine, Westmead Hospital, Sydney, Australia;University of Otago Christchurch, Christchurch, New Zealand;Victoria Transplant and Immunogenetics Service, Australian Red Cross Blood Service, West Melbourne, Victoria, Australia;

关键词: Kidney transplant;    Children;    Adolescents;    Parental donor;    Immunological profile;    Human leukocyte antigen;    Antibody;    Rejection;    Allograft loss;   

DOI  :  10.1186/s12882-021-02619-0

来源: Springer

【 摘 要 】

BackgroundParental 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.MethodsThis 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.DiscussionThe 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 registrationThe INCEPTION study has been registered with the Australian New Zealand Clinical Trials Registry, with the trial registration number of ACTRN12620000911998 (14th September 2020).

【 授权许可】

CC BY