North East Consortium for Transplant outcomes in APOL1 kidney Recipients (NECTAR) Clinical Center

项目摘要 APOL1风险变异(G1和G2)在非裔美国人中的患病率分别为30%和8% (AAS)，当处于纯合子状态时，通过以下方式增加非糖尿病终末期肾病的风险 7-10折。2014年进行了超过17,000例肾移植，其中AA占活体肾移植的11% 捐献者和14.2%的已故捐赠者。这项提议的目标是建立东北 APOL1肾移植受者移植结果联盟(NETAR)-临床中心，协作性组织 西奈山伊坎医学院和威尔·康奈尔医学中心之间的努力，包括2 协调中心、15个肾移植中心、9个组织相容性实验室、5个OPO和来自 UNOS，占纽约州所有移植的72%，占新泽西州所有移植的98%。这个 这一建议的理由如下：(1)不断发展的现有文献表明，活肾 捐赠者患慢性肾脏疾病(CKD)、高血压和蛋白尿的风险增加；(2)数据表明 在供者中存在2个APOL1风险变异时，死亡审查移植物丢失的风险增加；(3) 活体献血者APOL1基因变异与慢性肾脏病、高血压和 蛋白尿尚未出现特征；以及(4)再生障碍性贫血和西班牙裔患者临床结局的前瞻性研究。 活着的捐赠者和他们的接受者都缺乏。我们的具体目标确定了财团的主要组成部分， 即招募所有再生障碍性贫血捐赠者和非再生障碍性贫血捐赠者的接受者，从 参与中心，为期两年，研究APOL1基因对移植后的影响 结果，包括但不限于白蛋白/肌酐比率、估计的肾小球滤过率(EGFR) 以及移植物存活率。此外，非洲裔在世捐赠者将登记在世捐赠者和非再障捐赠者。 纵向追踪以确定载脂蛋白1风险变量在高血压、慢性肾脏病发展中的作用 和捐献后终末期肾病(ESRD)。捐赠者和受赠者都将被纵向跟踪 三年内，包括血液、尿液、粪便和活组织检查在内的生物检验品将被储存用于 进行生物测定以确定导致或触发肾功能下降的二次损害 要么是捐赠者，要么是接受者。将制定适当的议定书和程序，包括制定 一个基于网络的电子数据捕获工具，用于收集和跟踪来自研究参与者的数据和程序，以 确保安全、高效地将数据和标本传输到科学数据研究中心。

Project Summary APOL1 risk variants (G1 & G2) have a prevalence of 30% and 8%, respectively among African Americans (AAs), and when present in homozygous state, increase the risk of non-diabetic end-stage kidney disease by 7-10 fold. Over 17,000 kidney transplants were performed in 2014, for which AAs accounted for 11% of living donors and 14.2% of deceased donors. The objective of this proposal is to establish the North East Consortium for Transplant outcomes in APOL1 kidney Recipients (NECTAR)-Clinical Center, a collaborative effort between the Icahn School of Medicine at Mount Sinai and Weill Cornell Medical Center, comprising 2 coordinating centers, 15 kidney transplant centers, 9 histocompatibility labs, 5 OPOs and central support from UNOS, representing 72% of all transplants in New York State and 98% of all transplants in New Jersey. The rationale for this proposal includes the following: (1) evolving current literature suggests that living kidney donors are at increased risk for chronic kidney disease (CKD), hypertension and proteinuria; (2) data point to an increased risk of death-censored graft loss in the presence of 2 APOL1 risk variants in the donor; (3) the association of APOL1 gene variants in living donors with the development of CKD, hypertension and proteinuria has not been characterized; and (4) prospective studies of clinical outcomes in AA and Hispanic living donors and their recipients are lacking. Our Specific Aims define the key components of the Consortium, namely to recruit the recipients of all donors of AA and non-AA donors of African descent, from the participating centers, over a period of two years to study the impact of APOL1 genotype on post-transplant outcomes, including but not limited to albumin-to-creatinine-ratio, estimated glomerular filtration rate (eGFR) and graft survival. In addition, AA and non-AA donors of African descent living donors will be enrolled and followed longitudinally to determine the role of APOL1 risk variants in the development of hypertension, CKD and end stage renal disease (ESRD) post-donation. Both donors and recipients will be followed longitudinally for three years and biospecimens including blood, urine, stool and biopsies will be banked for the purpose of performing bioassays to identify secondary insults that contribute to or trigger the decline of renal function in either donors or recipients. Appropriate protocols and procedures will be established, including the creation of a web-based electronic data capture tool to collect and track data from research participants and procedures to ensure safe and efficient transfer of data and specimens to the Scientific Data Research Center.