Quantifying Risk And Survival Benefit from Incompatible Kidney Transplantation

量化不相容肾移植的风险和生存获益

• 批准号: 9442906
• 负责人: DORRY L. SEGEV
• 金额: $ 6.25万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9442906
• 关键词: Antibodies; Attenuated; Blood; Characteristics; Clinical; Counseling; Country; Data; Data Collection; Death Rate; Effectiveness; Engraftment; Factor Analysis; Future; Goals; Graft Survival; Growth; Kidney; Kidney Failure; Kidney Transplantation; Link; Modality; Modeling; Multivariate Analysis; Outcome; Outcome Study; Patient Selection; Patients; Phenotype; Postoperative Period; Procedures; Process; Protocols documentation; Publication Bias; Registries; Regression Analysis; Reporting; Research; Risk; Role; Source; Time; Transplantation; Treatment Protocols; Waiting Lists; candidate selection; cohort; comparative effectiveness; data registry; desensitization; evidence base; experience; graft function; improved; interest; multilevel analysis; novel; prospective; public health relevance; quality assurance; simulation; study population; transplant registry

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.

描述（由申请人提供）：每年，成千上万需要肾移植的患者找到活体捐赠者，但被降级而放弃活体捐赠者移植的好处 由于 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，超过 50% 的人不会通过 KPD 找到相容的匹配。如果不进行不相容活体肾移植 (ILDKT)，这些患者的唯一选择就是 90,000 名患者的已故捐献者等待名单，等待时间平均为 5-8 年，死亡率平均每年为 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来跨越抗体屏障接受移植。我们最近表明，美国有近 100 个中心进行 ILDKT，但很少有研究或报告其结果。虽然该领域最近取得了巨大进展，但未来的增长目前受到单中心报告的推论的限制，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方法是各中心共同研究结果，但数据收集负担是一个明显的问题。确实存在强制性的国家移植登记处，但未收集与 ILDKT 相关的数据。我们提出了一个大型、高效、混合的回顾性/前瞻性多中心链接，将负担最小的 ILDKT 特定原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) 确定与其他可用选择相比，从 ILDKT 中获得生存获益的患者； (3) 探索中心级与 ILDKT 结果的关联，包括中心与体积的关系。 尚无单中心研究能够研究 ILDKT 的风险预测。我们将收集大约 5800 名接受者的 ILDKT 特定数据，并链接到国家登记处，以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（即等待相容的已故捐赠者或 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推论与从 KPD 模拟中得出的推论相结合。我们将使用交互项分析来确定放大或减弱 ILDKT 对生存获益影响的因素。 这项研究将建立一个基于证据且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用于临床。在全国范围内更好地了解这种新兴模式将有助于提高 ILDKT 的可行性、可用性和质量，为数千名患者提供服务 谁可能从中受益。

项目成果

Early clinical complications after ABO-incompatible live-donor kidney transplantation: a national study of Medicare-insured recipients.

• DOI: 10.1097/tp.0000000000000029
• 发表时间: 2014-07-15
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Lentine KL;Axelrod D;Klein C;Simpkins C;Xiao H;Schnitzler MA;Tuttle-Newhall JE;Dharnidharka VR;Brennan DC;Segev DL
• 通讯作者: Segev DL

Where the Sun Shines: Industry's Payments to Transplant Surgeons.

阳光照耀的地方：行业支付给移植外科医生的费用。

• DOI: 10.1111/ajt.13427
• 发表时间: 2016
• 期刊: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
• 作者: Ahmed,R;Chow,EK;Massie,AB;Anjum,S;King,EA;Orandi,BJ;Bae,S;Nicholas,LH;Lonze,BE;Segev,DL
• 通讯作者: Segev,DL