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

总结/摘要 数据表明，来自非裔美国人（AA）已故供体的移植肾与以下疾病相关： 相对于来自非AA供体的肾脏，存活率降低。其他数据表明， APOL 1风险变异，仅在AA个体中发现，与风险增加有关。 一般AA人群中CKD/ESRD的发生率。该基因的两种风险变体在AA中的患病率为13%， 并可能导致移植失败的部分或全部风险增加。也有关于AA的轶事报道 具有两种APOL 1风险变体的活体肾脏捐献者发展为ESRD引起了进一步的关注。阿波罗 研究建议招募所有已故和活着的AA肾脏供体，以明确解决 APOL 1变异对肾移植结局的影响Emory APOLLO临床中心联盟由 分布在美国各地的12个中心，但集中在东南部。2015年，这12个项目被移植到 219个肾脏来自已故和活着的AA捐赠者，约占所有AA肾脏接受者的9%， 美国合格研究队列。我们的联合体的具体目标是：（1）进行APOL 1基因分型， 所有AA已故和活着的肾脏捐赠者，并为未来的研究建立样本库，以确定 是否额外的遗传因素有助于假定为风险表现所需的第二次打击， (2)比较AA供体的所有移植肾的存活率和功能，以确定 两种APOL 1风险变异对移植结果的影响，以及探索环境因素的可能性 （排斥、感染、合并症如高血压）提供第二次打击，以及3）研究 携带两个APOL 1变异基因拷贝的非裔美国人活体捐赠者是否有增加的风险， 治疗慢性肾病已故供体用于APOL 1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受体提供血液， 活体捐赠者（必要时也包括已故捐赠者）。人口统计学和临床供体和受体 UNOS将提供所有受试者的数据。将为患者提供更详细的临床数据 接受12个参与移植中心之一的长期随访。我们建议 受试者1年，并对其进行3年随访，从而最大限度地提高观察临床 事件死亡供肾受者的主要结局指标是移植物存活率， 次要结局指标评估各种肾功能和损伤指标。提前CKD 或终末期肾病后的活体肾脏捐赠是极不可能的事件，考虑到相对较短的研究持续时间， 活体供肾者的主要结局是肾功能相对于移植后基线的变化 到捐献后3年随访结束。当与其他14个APOLLO的数据相结合时 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 APOL 1基因变异对肾移植和捐赠结果的影响

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.