PDF(Pubmed)
Abstract：
The diagnosis of acute T cell-mediated rejection (aTCMR) after kidney transplantation has considerable relevance for research purposes. Its definition is primarily based on tubulointerstitial inflammation and has changed little over time; aTCMR is therefore a suitable parameter for longitudinal data comparisons. In addition, because aTCMR is managed with antirejection therapies that carry additional risks, anxieties, and costs, it is a clinically meaningful endpoint for studies. This paper reviews the history and classifications of TCMR and characterizes its potential role in clinical trials: a role that largely depends on the nature of the biopsy taken (indication vs protocol), the level of inflammation observed (e.g., borderline changes vs full TCMR), concomitant chronic lesions (chronic active TCMR), and the therapeutic intervention planned. There is ongoing variability-and ambiguity-in clinical monitoring and management of TCMR. More research, to investigate the clinical relevance of borderline changes (especially in protocol biopsies) and effective therapeutic strategies that improve graft survival rates with minimal patient morbidity, is urgently required. The present paper was developed from documentation produced by the European Society for Organ Transplantation (ESOT) as part of a Broad Scientific Advice request that ESOT submitted to the European Medicines Agency for discussion in 2020. This paper proposes to move toward refined definitions of aTCMR and borderline changes to be included as primary endpoints in clinical trials of kidney transplantation.
摘要：
肾移植后急性T细胞介导的排斥反应（aTCMR）的诊断与研究目的具有相当大的相关性。它的定义主要基于肾小管间质炎症，并且随时间变化不大；因此，aTCMR是纵向数据比较的合适参数。此外,因为aTCMR是用带有额外风险的抗排斥疗法来管理的，焦虑,和成本，这是一个有临床意义的研究终点.本文回顾了TCMR的历史和分类，并描述了其在临床试验中的潜在作用：这种作用在很大程度上取决于所采取的活检的性质（适应症与方案），观察到的炎症水平(例如，边界线变化与完整TCMR），伴随慢性病变（慢性活动性TCMR），和计划的治疗干预。TCMR的临床监测和管理存在持续的可变性和模糊性。更多研究,研究临界变化的临床相关性（特别是在协议活检中）和有效的治疗策略，以提高移植物存活率和最低的患者发病率，迫切需要。本文是根据欧洲器官移植学会（ESOT）编写的文档开发的，作为ESOT在2020年提交给欧洲药品管理局讨论的广泛科学建议要求的一部分。本文建议朝着完善的aTCMR定义和边界线变化的方向发展，以作为肾移植临床试验的主要终点。
