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

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

doi:10.1186/s12882-021-02619-0

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 Nephrol. 2021 Dec 19;22(1):416. doi: 10.1186/s12882-021-02619-0.

Authors

Wai H Lim^{1

2}, Brigitte Adams³, Stephen Alexander^{4

5}, Antonia H M Bouts⁶, Frans Claas⁷, Michael Collins^{8

9}, Elisabeth Cornelissen¹⁰, Heather Dunckley¹¹, Huib de Jong¹², Lloyd D'Orsogna^{13

14

15}, Anna Francis^{16

17}, Sebastiaan Heidt⁷, Jean Herman¹⁸, Rhonda Holdsworth¹⁹, Joshua Kausman^{20

21

22}, Rabia Khalid^{23

24}, Jon Jin Kim^{25

26

27}, Siah Kim⁴, Noël Knops^{18

28}, Vasilis Kosmoliaptsis^{29

30

31}, Cynthia Kramer⁷, Dirk Kuypers^{32

33}, Nicholas Larkins^{34

24

35}, Suetonia C Palmer³⁶, Chanel Prestidge³⁷, Agnieszka Prytula³⁸, Ankit Sharma^{24

39}, Meena Shingde⁴⁰, Anne Taverniti²⁴, Armando Teixeira-Pinto²³, Peter Trnka^{16

17}, Francis Willis^{34

35

41}, Daniel Wong^{34

42}, Germaine Wong^{23

24

39}

Affiliations

¹ Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, 6009, Australia. [email protected].
² Medical School, University of Western Australia, Perth, Australia. [email protected].
³ Department of Pediatric Nephrology, Hôpital Universitaire des Enfants-Reine Fabiola, Brussels, Belgium.
⁴ Department of Nephrology, Westmead Children's Hospital, Sydney, Australia.
⁵ Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
⁶ Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam University Medical Center, Amsterdam, The Netherlands.
⁷ Department of Immunology, Leiden University Medical Centre, Leiden, The Netherlands.
⁸ Department of Renal Medicine, Auckland District Health Board, Auckland City Hospital, Auckland, New Zealand.
⁹ Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
¹⁰ Department of Pediatric Nephrology, Radboud University Medical Center, Amalia Children's Hospital, Nijmegen, The Netherlands.
¹¹ New Zealand Transplantation and Immunogenetics Laboratory, New Zealand Blood Service, Auckland, New Zealand.
¹² Erasmus Medical Center, Rotterdam, The Netherlands.
¹³ Faculty of Health and Medical Sciences, Pathology & Laboratory Medicine, University of Western Australia, Perth, Australia.
¹⁴ Department of Clinical Immunology, Fiona Stanley Hospital, Perth, Australia.
¹⁵ National Pancreas Unit, Westmead Hospital, Sydney, Australia.
¹⁶ School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
¹⁷ Child and Adolescent Renal Service, Children's Health Queensland, Brisbane, Queensland, Australia.
¹⁸ Department of Pediatric Nephrology and Solid Organ Transplantation, University Hospitals Leuven, Leuven, Belgium.
¹⁹ Victoria Transplant and Immunogenetics Service, Australian Red Cross Blood Service, West Melbourne, Victoria, Australia.
²⁰ Department of Nephrology, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
²¹ Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
²² University of Melbourne, Melbourne, Victoria, Australia.
²³ Sydney School of Public Health, The University of Sydney, Sydney, Australia.
²⁴ Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Sydney, Australia.
²⁵ Department of Paediatric Nephrology, Nottingham University Hospital, Nottingham, UK.
²⁶ Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, WC1N 3JH, UK.
²⁷ MRC Centre for Transplantation, Guy's Hospital, London, UK.
²⁸ Department of Development and Regeneration (Woman and Child), KU Leuven, Leuven, Belgium.
²⁹ Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
³⁰ UK and NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, University of Cambridge, Hills Road, Cambridge, UK.
³¹ NIHR Cambridge Biomedical Research Centre, Hills Road, Cambridge, UK.
³² Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.
³³ Department of Microbiology and Immunology, KU Leuven, University of Leuven, Leuven, Belgium.
³⁴ Medical School, University of Western Australia, Perth, Australia.
³⁵ Department of Nephrology, Perth Children's Hospital, Perth, Australia.
³⁶ University of Otago Christchurch, Christchurch, New Zealand.
³⁷ Starship Children's Hospital, Auckland Health Board, Auckland, New Zealand.
³⁸ Department of Pediatric Nephrology and Rheumatology, Ghent University Hospital, Ghent, Belgium.
³⁹ Department of Renal Medicine, Westmead Hospital, Sydney, Australia.
⁴⁰ NSW Health Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, Sydney, Australia.
⁴¹ School of Medicine, University of Notre Dame (Fremantle), Perth, Australia.
⁴² Anatomical Pathology, PathWest, QEII Medical Centre, Perth, Australia.

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).

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

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Child
Donor Selection*
Histocompatibility*
Humans
Kidney Transplantation*
Patient Selection*
Risk Assessment
Treatment Outcome