Quantifying Risk And Survival Benefit from Incompatible Kidney Transplantation

描述（由申请人提供）：每年，成千上万的需要肾移植的患者找到了活体供体，但却放弃了活体供体移植的益处 因为ABO或HLA不相容。他们可以参与肾脏配对捐赠（KPD，也称为肾脏交换或链），但由于广泛的HLA致敏或难以匹配的血型，>50%的人无法通过KPD找到相容的匹配。如果没有不相容的活体供肾移植（ILDKT），这些患者的唯一选择是90，000名患者的死亡供体等待名单，等待时间平均为5-8年，死亡率平均为每年5-10%。 ILDKT是一种新兴的实践，患者可以通过使用各种术前和术后脱敏策略接受跨越抗体屏障的移植。我们最近发现，在美国有近100个中心进行了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的进展，但未来的增长目前受到单中心报告推断的限制，这些报告存在出版偏倚、缺乏统计效力、无法比较单中心内的方案有效性（因为给定中心内的方案同质性）以及缺乏普遍性。 推动这一领域向前发展的唯一途径是各中心合作研究结果，但数据收集负担是一个明显的问题。一个强制性的国家移植登记处确实存在，但没有收集与ILDKT相关的数据。我们提出了一个大的、高效的、混合回顾性/前瞻性的多中心链接，将最小负担的ILDKT特异性原始数据与丰富的、纵向的国家登记数据联系起来，通过该链接，我们可以：（1）量化与ILDKT结局相关的患者、抗体和治疗方案因素;（2）识别与其他可用选择相比从ILDKT获得生存获益的患者;以及（3）探索中心水平与ILDKT结局的相关性，包括中心容量关系。 尚无单中心研究可用于研究ILDKT的风险预测。我们将收集大约5800名ILDKT接受者的特定数据，并链接到国家登记处，对与结果相关的因素进行多变量分析。为了将ILDKT与其他可用选项（即等待相容的已故供体或KPD）进行比较，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中得出的联合收割机推断与从KPD模拟中得出的推断相结合。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。 这项研究将建立一个以证据为基础的、符合患者最佳利益的ILDKT患者选择和咨询框架。与ILDKT相关的风险和生存获益的稳健量化是新颖的，将立即在全国范围内临床使用。在全国范围内更好地了解这种新兴的治疗方式，将有助于提高ILDKT的可行性、可用性和质量， 谁能从中受益。

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.