Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, 6009, Australia.
Medical School, University of Western Australia, Perth, Australia.
BMC Nephrol. 2021 Dec 19;22(1):416. doi: 10.1186/s12882-021-02619-0.
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.
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.
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.
The INCEPTION study has been registered with the Australian New Zealand Clinical Trials Registry, with the trial registration number of ACTRN12620000911998 (14th September 2020).
对于肾衰竭的儿童和青少年来说，父母供体肾移植是最常见的治疗选择。来自观察性研究的新数据报告称，与母亲供体相比，父亲供体的受者短期和中期移植物结局得到改善。INCEPTION 研究旨在确定母亲和父亲供体肾脏之间免疫相容性的潜在差异，并确定这如何影响肾衰竭的儿童和青少年的肾脏移植物结局。
这项纵向观察性研究将招募年龄≤18 岁的接受父母供体肾移植的肾移植受者，这些受者在 1990 年至 2020 年期间在 4 个国家（澳大利亚、新西兰、英国和荷兰）接受了肾移植。将对受者和相应的父母供体进行高分辨率人类白细胞抗原（HLA）分型，以深入评估免疫相容性。主要结局是新出现的供体特异性抗 HLA 抗体（DSA）、经活检证实的急性排斥反应或移植后 60 个月内的移植物丢失的复合终点。次要结局是新出现的 DSA、经活检证实的急性排斥反应、移植后肾活检上急性或慢性抗体介导的排斥反应或慢性移植物损伤指数（CADI）评分>1、移植物功能、蛋白尿和移植物丢失。使用主成分分析和 Cox 比例风险回归模型，我们将确定定义的免疫和临床参数集之间的关联，这些关联可能确定接受父母供体肾移植的年轻人的主要和次要结局的风险分层。这种研究设计将使我们能够专门研究接受母亲供体与接受父亲供体相比，对于决定供体选择的家庭来说，母亲供体的潜在免疫风险。
INCEPTION 研究的结果将探讨儿童和青少年接受父母供体肾移植时母亲和父亲供体的肾脏潜在的免疫风险差异。我们的研究将为选择父母供体提供证据基础，以实现儿童和青少年的最佳长期肾移植和整体健康结局，儿童和青少年是一个公认的弱势群体。
INCEPTION 研究已在澳大利亚和新西兰临床试验注册处注册，试验注册号为 ACTRN12620000911998（2020 年 9 月 14 日）。
