Quantifying Risk And Survival Benefit from Incompatible Kidney Transplantation

描述(申请人提供)：每年，数以千计的需要肾移植的患者找到活体捐赠者，但被降级为放弃活体捐赠者移植的好处 因为ABO或人类白细胞抗原不相容。他们可以参与肾脏配对捐献(KPD，也称为肾脏交换或肾脏链)，但由于广泛的HLA致敏或难以匹配的血型，50%的人将无法通过KPD找到相容的匹配。如果没有血型不合的活体肾移植(ILDKT)，这些患者唯一的选择是9万名已故供者等待名单，等待时间平均为5-8年，死亡率平均为每年5-10%。ILDKT是一种新兴的做法，患者可以通过使用各种术前和术后脱敏策略，跨越抗体屏障接受移植。我们最近显示，在美国有近100个中心进行ILDKT，尽管很少有人研究或报告他们的结果。虽然最近在这一领域取得了很大进展，但未来的增长目前受到单中心报告的推断的限制，这些报告存在发表偏差、缺乏统计能力、无法比较单中心内的协议有效性(因为给定中心内的协议同质性)以及缺乏泛化能力。推动这一领域向前发展的唯一方法是让中心合作研究结果，但数据收集负担是一个明显的担忧。确实存在强制的国家移植登记，但没有收集与ILDKT相关的数据。我们提出了一个大规模、高效、混合的多中心联系，将负担最小的ILDKT特定的初始数据与丰富的纵向国家登记数据联系起来，通过它，我们可以：(1)量化与ILDKT结果相关的患者、抗体和治疗方案因素；(2)与其他可用的选择相比，识别从ILDKT获得生存益处的患者；以及(3)探索中心水平与ILDKT结果的关联，包括中心-容量关系。目前还没有单中心研究来研究ILDKT的风险预测。我们将收集大约5800名受助者的ILDKT特定数据，并链接到国家登记，以进行与结果相关的因素的多变量分析。为了将ILDKT与其他可用的选择进行比较，即等待相容的已故捐赠者或KPD，我们将使用马尔可夫决策过程模型，该模型将从等待名单的观察数据得出的推论与从KPD的模拟得出的推论相结合。我们将使用交互作用项分析来确定放大或减弱ILDKT对生存益处的影响的因素。这项研究将为ILDKT的患者选择和咨询建立一个以证据为基础的、符合患者最佳利益的框架。对与ILDKT相关的风险和生存益处进行强有力的量化是新颖的，并将立即在全国范围内用于临床。在国家、可推广的水平上更好地了解这一新兴模式将有助于提高每个患者接受ILDKT的可行性、可用性和质量 谁有可能从中受益。

DESCRIPTION (provided by applicant): Every year, thousands of patients in need of a kidney transplant find a live donor but are relegated to forego the benefits of live donor transplantation because of ABO or HLA incompatibilities. They can participate in kidney paired donation (KPD, also called kidney exchanges or chains), but >50% will not find a compatible match through KPD due to broad HLA sensitization or hard-to-match blood types. Without incompatible live donor kidney transplantation (ILDKT), the only option for these patients is the 90,000-patient deceased donor waiting list, where waiting times average 5-8 years and death rates average 5-10% per year. ILDKT is an emerging practice in which patients can receive transplants across antibody barriers through the use of various pre- and post-operative desensitization strategies. We recently showed that close to 100 centers perform ILDKT in the US, although few have studied or reported their outcomes. While great gains have been recently made in this field, future growth is currently limited by inferences from single-center reports which suffer from publication bias, lack of statistical power, inability to compare protocol effectiveness within a single-center (because of protocol homogeneity within a given center), and lack of generalizability. The only way to move this field forward is for centers to study outcomes collaboratively, but data collection burden is an obvious concern. A mandated, national transplant registry does exist, but data relevant to ILDKT are not collected. We propose a large, highly efficient, mixed retrospective/prospective multi-center linkage of minimal-burden ILDKT-specific primary data to rich, longitudinal national registry data, through which we can: (1) quantify patient, antibody, and treatment protocol factors associated with ILDKT outcomes; (2) identify patients who derive survival benefit from ILDKT compared with other available options; and (3) explore center-level associations with ILDKT outcomes, including center-volume relationships. No single-center studies have been powered to study risk prediction in ILDKT. We will collect ILDKT- specific data of approximately 5800 recipients and link to the national registry for multivariate analyses of factors associated with outcomes. To compare ILDKT with the other available options, i.e. waiting for a compatible deceased donor or KPD, we will use a Markov decision process model that combine inferences drawn from observational data of the waiting list with inferences drawn from simulations of KPD. We will use interaction term analysis to identify factors that amplify or attenuate the effect of ILDKT on survival benefit. This researh will establish a framework for patient selection and counseling for ILDKT that is evidence- based and in the best interest of patients. Robust quantification of the risk and survival benefit associated with ILDKT is novel and will be immediately useable clinically throughout the country. A better understanding of this emerging modality at a national, generalizable level will help improve the feasibility, availability, and quality of ILDKT for the thousands of patients each year who could potentially benefit from it.