Development of a National Incompatible Kidney Transplant Registry

描述(由申请人提供)： 本申请涉及广泛的挑战领域(07)增强临床试验和特定挑战主题，07-DK-103：对注册的支持。活体供肾移植是治疗肾衰竭的最佳方法，可使预期寿命延长一倍，并显著提高生活质量。然而，据估计，每年有2000-4000名患者找到一个健康的、自愿的活体捐赠者，但由于他们与捐赠者的ABO或HLA血型不合，他们被降级为放弃活体肾移植的好处。其中一些患者可能通过配对肾脏捐献找到相合的配型，但那些具有广泛的人类白细胞抗原敏感性或血型难以匹配的患者(超过50%的配对不相容)将无法通过配对捐献找到匹配。如果没有血型不合的肾移植(IKT)，这些患者唯一的另一个选择是加入8万名已故捐赠者的等待名单，等待时间平均为5-7年，透析死亡率每年超过10%。IKT是一种新兴的实践，通过使用各种脱敏技术，患者可以跨越抗体屏障接受肾移植。在美国，每年大约有200例这样的移植手术，其中大约三分之一是由少数几个大容量中心进行的，三分之二分布在大约90个其他非常低容量的中心。然而，目前有两大挑战限制了IKT领域的未来增长。首先，非常需要研究和验证当前议定书的具体组成部分，并制定最佳做法。只有以前瞻性的方式从多个中心收集足够、详细的数据，才能做到这一点；到目前为止，只有单中心的研究可供分析。其次，由于IKT依赖于免疫遗传学和病理学方面的新技术，因此很难实施，因此非常需要更有经验的中心来指导新的提供者团队。目前，由于不能很容易地共享详细的、综合的、纵向的临床、组织学、放射学和免疫学数据，这一点受到了限制。为了更好地了解IKT，并指导建立这些项目的新中心，我们建议开发一个国家不相容肾脏移植注册中心。我们将根据对目前参与这一程序的人员进行的一系列系统深入访谈来设计这一登记表，然后扩展目前现有的关系型患者管理软件以适应该登记处的需要。然后，我们将对我们中心的追溯性病例、我们中心的预期病例以及来自全国几个中心的预期病例进行试点测试。最后，我们将制定可持续发展的长期计划。对于致敏患者，IKT往往是唯一可行的治疗方案，与次佳方案相比，IKT为这些患者提供了显著(3倍以上)的生存益处，即等待已故供者等待相容供者。扩大这一治疗模式不仅将挽救生命，减少漫长的等待名单，并为美国医疗系统节省大量成本，而且还将刺激全国范围内移植中心、组织分型实验室和病理实验室的扩张。虽然活体供肾移植是治疗肾衰竭的最佳方法，但每年仍有数以千计的患者拥有健康、自愿的供者，但由于供者与供者血型不合，他们被降级为放弃了活体供者移植的好处。血型不合的肾移植是一种新兴的做法，患者可以接受血型不合的捐赠者的肾移植，但到目前为止，这一领域仅限于单中心经验，方案无法得到验证，最佳实践无法开发，更有经验的中心无法完成对新中心的指导。该项目的目标是创建一个详细的、集成的、全国不相容的肾脏移植登记系统，它将以一种极大地改善和扩大不相容肾脏移植的方式，将全美多个中心的临床、活检、放射学和抗体数据联系起来。

DESCRIPTION (provided by applicant): Summary This application addresses broad Challenge Area (07) Enhancing Clinical Trials and specific Challenge Topic, 07-DK-103: Support for Registries. Live donor kidney transplantation is the best treatment for kidney failure, doubling life expectancy and significantly improving quality of life. However, it is estimated that 2000-4000 patients every year find a healthy, willing live donor but are relegated to forego the benefits of live donor renal transplantation because they are ABO or HLA incompatible with their donor. Some of these patients might find compatible matches through kidney paired donation, but those with broad HLA sensitization or hard-to-match blood types (over 50% of incompatible pairs) will not find matches through paired donation. Without incompatible kidney transplantation (IKT), the only other option for these patients is to join the 80,000-patient deceased donor waiting list, where waiting times average 5-7 years and death rates on dialysis exceed 10% per year. IKT is an emerging practice in which patients can receive kidney transplants across antibody barriers through the use of various desensitization techniques. Approximately 200 of these transplants are performed annually in the United States, of which approximately one-third are performed by a handful of high-volume centers and two-thirds are scattered across approximately 90 other very low-volume centers. However, two major challenges currently limit future growth in the field of IKT. First, there is a great need to study and validate specific components of the current protocols and develop best practice. This can only be accomplished if sufficient, detailed data from multiple centers can be collected in a prospective fashion; to date, only single-center studies have been available for analysis. Second, because IKT can be hard to implement due to its reliance on new technology in immunogenetics and pathology, there is a great need for mentoring of new provider teams by more experienced centers. This is currently limited by the inability to readily share detailed, integrated, longitudinal clinical, histological, radiographic, and immuogenetics data. In an effort to better understand IKT and mentor new centers building these programs, we propose to develop a National Incompatible Kidney Transplant Registry. We will design this registry based on a systematic set of in-depth interviews with personnel currently involved in this procedure, and then extend currently existing relational patient management software to accommodate the needs of this registry. We will then pilot test the registry on retrospective cases at our center, prospective cases at our center, and prospective cases from a handful of centers around the country. Finally, we will develop a long-term plan for sustainability. For sensitized patients, IKT is often the only viable treatment option, providing a significant (more than 3- fold) survival benefit to these patients when compared to the next-best available option, namely waiting on the deceased donor waiting list for a compatible donor. Expanding this treatment modality will not only save lives, decrease the long waiting list, and save the US healthcare system significant costs, but will also stimulate the expansion of transplant centers, tissue typing labs, and pathology labs nationwide. Although live donor kidney transplantation is the best treatment for kidney failure, thousands of patients each year have a healthy, willing donor but are relegated to forego the benefits of live donor transplantation because they are incompatible with their donor. Incompatible kidney transplantation is an emerging practice in which patients can receive kidney transplants from their incompatible donors, but this field has thus far been limited to single-center experiences where protocols cannot be validated, best practice cannot be developed, and mentorship of new centers by more experienced centers cannot be accomplished. The goal of this project is to create a detailed, integrated, National Incompatible Kidney Transplant Registry that will link clinical, biopsy, radiology, and antibody data from multiple centers throughout the United States in a way that will greatly improve and expand incompatible kidney transplantation.