A trial of transplanting Hepatitis C-viremic kidneys into Hepatitis C-Negative kidney recipients (THINKER-NEXT)

项目概要/摘要 肾移植延长了生命，提高了生活质量，降低了医疗费用。不幸的是，等待 名单超过94，000人，而只有大约14，000名死者供体肾移植（DDKT）发生 每年，许多患者等待DDKT>5年。对于老年人和其他一些患者群体来说， 等待死亡是很常见的然而，近600个来自感染丙型肝炎病毒（HCV）的捐赠者的肾脏被丢弃， 2018年（来自HCV病毒血症供体的肾脏总数的50.1%）;数百个肾脏从未被移植 因为他们认为没有一个中心会接受他们。试点临床试验的早期成功， 单中心系列HCV病毒血症供体的移植肾已经证明了这一潜力 每年增加1,000多例肾脏移植手术， 年然而，用于评估肾脏质量的主导系统也将较低的质量评分应用于任何肾脏。 来自HCV病毒血症供体的肾脏，从而促进器官丢弃。此外，早期的经验 没有匹配良好的对照组的非对照研究导致了意外并发症的报告 和/或高于预期的治疗失败率，强调需要正式的多中心 临床试验最近的报告强调了一系列移植后并发症， 在一项大型多中心试验中进行评估，例如：a）在几个HCV阴性患者中， HCV-病毒血症供体的受体; B）HCV-病毒血症供体的受体中CMV病毒血症的发生率增加 肾;和c）膜增生性肾小球肾炎。虽然这些并发症很罕见，但它们强调了 移植领导者的观点，包括美国移植协会，美国移植协会， 肝脏疾病研究和美国传染病学会认为这种做法被认为是 “实验性”，最好在IRB批准的方案下进行，并获得严格的知情同意， 确保获得HCV治疗。此外，尽管从HCV- 病毒血症供体转化为HCV阴性患者，仍然存在需要解决的持续知识差距 从患者、提供者和支付者的角度来看，这种做法被接受为常规临床护理。 这项多中心试验旨在通过解决这些具体问题， 目的：a）估计HCV-病毒血症肾的HCV阴性受者的HCV治愈率， 间隔; B）确定同意接受HCV病毒血症肾是否改善存活; c）评估1- 与匹配的对照物相比，HCV病毒血症肾的年肾功能; d）评估HCV- HCV-病毒血症肾的阴性接受者具有增加的CMV感染风险;和e）确定 HCV病毒血症与HCV阴性供肾者中慢性肾病病理学的患病率相似。的 首要目标是确定HCV病毒血症供体的肾脏是否可以安全地移植到HCV- 终末期肾病阴性患者。

Project Summary/Abstract Kidney transplant extends life, improves quality of life, and reduces healthcare costs. Unfortunately, the waiting list exceeds 94,000 people while only approximately 14,000 deceased donor kidney transplants (DDKT) occur annually and many patients wait >5 years for a DDKT. For the elderly and some other patient groups, it is common to die waiting. Yet, nearly 600 kidneys from donors infected hepatitis C virus (HCV) were discarded in 2018 (50.1% of the total number of kidneys from HCV-viremic donors); hundreds more kidneys are never procured because of the perception that no center will accept them. Early successes of pilot clinical trials and single-center series of transplanting kidneys from HCV-viremic donors have demonstrated the potential for this practice to increase the number of lifesaving kidney transplants by more than 1,000 kidney transplants each year. However, the dominant system for assessing kidney quality also applies a lower quality score to any kidney from an HCV-viremic donor, thereby promoting organ discard. Also, early experiences from uncontrolled studies without well-matched comparator groups has led to reports of unexpected complications and/or higher than anticipated rates of treatment failures that underscore the need for a formal multi-center clinical trial. Recent reports have highlighted a series of post-transplant complications that necessitate evaluation in a large multi-center trial, for example: a) fibrosing cholestatic HCV in several HCV-negative recipients of an HCV-viremic donor; b) increased incidence of CMV viremia in recipients of HCV-viremic kidneys; and c) membranoproliferative glomerulonephritis. While these complications are rare, they underscore the view from transplant leaders, including the American Society of Transplantation, the American Association for the Study of Liver Diseases, and the Infectious Disease Society of America that this practice is considered `experimental' and is best performed under IRB-approved protocols with rigorous informed consent and assurances of access to HCV treatment. Furthermore, despite increased transplantation of kidneys from HCV- viremic donors into HCV-negative patients, there remain persistent knowledge gaps that need to be addressed for this practice to be accepted as routine clinical care from the perspective of patients, providers, and payers. This multi-center trial seeks to provide significant knowledge gaps that remain by addressing these specific aims: a) estimate HCV cure rates in HCV-negative recipients of HCV-viremic kidneys with a narrow confidence interval; b) determine whether consenting to receiving an HCV-viremic kidney improves survival; c) evaluate 1- year renal function of HCV-viremic kidneys compared to matched comparators; d) assess whether HCV- negative recipients of HCV-viremic kidneys have increased risks of CMV infection; and e) determine if the prevalence of chronic kidney disease pathology is similar in HCV-viremic vs HCV-negative kidney donors. The overarching goal is to determine if kidneys from HCV-viremic donors can safely be transplanted into HCV- negative patients with end-stage renal disease.