Studying APOL1 Following Transplantation (SAF-T): the Emory APOLLO Clinical Center Consortium

摘要/摘要 数据显示，来自非裔美国人(AA)已故捐赠者的移植肾脏与 与非再生障碍性贫血供者的肾脏相比，存活率降低。更多的数据表明，有两个 仅在再生障碍性贫血患者中发现的APOL1风险变异与风险增加有关 CKD/ESRD在普通再障人群中的分布。该基因的两个风险变种在AAS中的患病率为13%， 这可能是移植失败风险增加的部分或全部原因。也有一些关于AA的轶事报道 具有两个APOL1风险变异的活体肾脏捐赠者罹患终末期肾病的风险增加了进一步的担忧。阿波罗号 研究建议招募所有已故和在世的AA肾脏捐赠者，以明确解决 APOL1变异对肾移植结果的影响。埃默里·阿波罗临床中心财团由 12个中心分布在美国各地，但主要集中在东南部。2015年移植了这12个项目 219个来自已故和在世AA捐赠者的肾脏，约占所有AA肾脏受者的9%， 在美国符合条件的研究队列。我们联盟的具体目标是：(1)进行APOL1基因分型 所有AA已故和在世的肾脏捐赠者，并创建一个样本库，以供未来的研究确定 额外的遗传因素是否有助于第二次命中被认为是风险表现所必需的， (2)比较所有AA供者移植肾的存活和功能，以确定 两个APOL1风险变异对移植结果的影响以及探索环境因素的潜力 (排斥、感染、高血压等共病)提供第二次打击，以及3)研究 携带两份APOL1变异基因的活着的非裔美国人捐赠者是否面临更高的风险 治疗慢性肾脏疾病。为已故献血者进行APOL1基因分型的血液样本将由 器官采购组织，而移植中心将为基因分型接受者提供血液，并 在世捐赠者(必要时也包括已故捐赠者)。人口统计和临床供受者 联合国内罗毕办事处将提供所有科目的数据。将为患者提供更细粒度的临床数据 从12个参与移植中心之一接受他们的长期随访。我们建议招收 受试者1年，随访3年，从而最大限度地增加观察临床的可能性 事件。衡量已故供者肾脏受者的主要预后指标是移植肾存活率 评估肾功能和损伤的各种指标的次要结果指标。作为高级CKD 考虑到研究持续时间相对较短，活体肾脏捐赠后发生ESRD或ESRD的可能性极小 活体肾脏捐献者的主要结局将是移植后肾功能的变化。 至术后3年随访结束。与其他14艘阿波罗飞船的数据结合在一起 临床中心联盟，我们相信我们的数据将有助于更全面地了解 载脂蛋白1基因变异对肾移植和捐献结局的影响

Summary/Abstract Data demonstrate that transplanted kidneys from African American (AA) deceased donors are associated with reduced survival relative to kidneys from non-AA donors. Additional data demonstrate that the presence of two APOL1 risk variants, that are found exclusively in AA individuals, have been associated with an increased risk of CKD/ESRD in the general AA population. Two risk variants of this gene have a prevalence of 13% in AAs, and may account for some or all of the increased risk of transplant loss. There are also anecdotal reports of AA living kidney donors with two APOL1 risk variants developing ESRD raising further concerns. The APOLLO study proposes to enroll all deceased and living AA kidney donors in order to definitively address the impact of APOL1 variants on kidney transplant outcomes. The Emory APOLLO Clinical Centers consortium is comprised of 12 centers distributed across the US but focused in the Southeast. In 2015 these 12 programs transplanted 219 kidneys from deceased and living AA donors accounting for about 9% of all recipients of AA kidneys, the eligible study cohort in the US. The specific aims of our consortium are: (1) to perform APOL1 genotyping on all AA deceased and living kidney donors and create a sample repository for future studies to determine whether additional genetic factors contribute to the second hit postulated to be required for risk manifestation, (2) to compare the survival and function of all transplanted kidneys from AA donors to determine the impact of two APOL1 risk variants on transplant outcomes as well as exploring the potential of environmental factors (rejection, infections, comorbid conditions such as hypertension) to provide the second hit, and 3) to study whether African American living donors who carry two copies of the variant APOL1 genes are at increased risk for chronic kidney disease. Blood samples for APOL1 genotyping of deceased donors will be provided by the organ procurement organization, while the transplant centers will provide blood for genotyping recipients and living donors (as well as deceased donors when necessary). Demographic and clinical donor and recipient data will be provided by UNOS for all subjects. More granular clinical data will be provided for patients receiving their long-term follow up from one the 12 participating transplant centers. We propose enrolling subjects for 1 year and following them for 3 years thereby maximizing the likelihood of observing clinical events. The primary outcome measure for recipients of deceased donor kidneys is graft survival with secondary outcome measures assessing a variety of indicators of renal function and injury. As advance CKD or ESRD following living kidney donation are highly unlikely events, given the relatively short study duration the primary outcome for living kidney donors will be the change in renal function from the post-transplant baseline to the end of follow up at 3 years post-donation. When combined with the data from the other 14 APOLLO Clinical Center Consortia, we believe our data will contribute to a much more complete understanding of the impact of APOL1 gene variants on the outcomes of kidney transplantation and donation.