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

APOL1 肾移植结果东北联盟 (NECTAR) 临床中心

• 批准号: 9980194
• 负责人: Darshana Dadhania
• 金额: $ 17.13万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9980194
• 关键词: Acute; Affect; African; African American; Albumins; Allografting; Ancillary Study; Apolipoproteins; Biological; Biological Assay; Biopsy; Blood; Center for Translational Science Activities; Chronic Kidney Failure; Clinical; Clinical Data; Clinical Pathology; Clinical Sciences; Collaborations; Collection; Consent; Creatinine; DNA; Data; Data Collection; Databases; Development; Diabetes Mellitus; Donor person; End stage renal failure; Enrollment; Ensure; Event; Feces; Focal Segmental Glomerulosclerosis; Genes; Genetic; Genetic study; Genomics; Genotype; Glomerular Filtration Rate; Graft Survival; HIV; Hispanics; Histocompatibility; Hypertension; Immune response; Immunosuppression; Incidence; Infection; Kidney; Kidney Failure; Kidney Transplantation; Laboratories; Link; Literature; Living Donors; Longterm Follow-up; Management Information Systems; Medical center; New Jersey; New York; Online Systems; Outcome; Outpatients; Participant; Pathologic; Patients; Pharmaceutical Preparations; Predisposition; Prevalence; Procedures; Prospective Studies; Proteinuria; Protocols documentation; Renal function; Research; Risk; Risk Factors; Role; Sampling; Shipping; Site; Specimen; Stratification; Surveys; Testing; Transplant Recipients; Transplantation; United Network for Organ Sharing; Urine; Visit; Withdrawal; Work; central database; clinical center; data exchange; data integrity; electronic data; follow-up; genetic variant; high risk; kidney allograft; living kidney donor; medical schools; mortality risk; non-diabetic; post-transplant; programs; prospective; recruit; risk variant; shared database; tool; transplant centers

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.

项目摘要 APOL 1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)，并且当以纯合子状态存在时，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占存活率的11% 捐赠者和14.2%的已故捐赠者。该提案的目标是建立东北 APOL 1肾受体移植结局联盟（NECTAR）-临床中心，一个合作组织 西奈山伊坎医学院和威尔康奈尔医疗中心之间的努力，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%和新泽西州所有移植的98%。的 该建议的基本原理包括以下内容：（1）不断发展的现有文献表明， 献血者患慢性肾病（CKD）、高血压和蛋白尿的风险增加;（2）数据表明， 在供体中存在2种APOL 1风险变体的情况下，死亡删失移植物丢失的风险增加;（3） 活体供者APOL 1基因变异与CKD、高血压和 蛋白尿的特征尚未明确;（4）对AA和西班牙裔患者的临床结局进行前瞻性研究 缺乏活体捐赠者和接受者。我们的具体目标定义了联盟的关键组成部分， 即招募所有AA捐赠者和非AA捐赠者的非洲裔接受者， 参与中心，在两年的时间内研究APOL 1基因型对移植后 结局，包括但不限于白蛋白/肌酐比值、估计肾小球滤过率（eGFR） 和移植物存活率。此外，将招募AA和非AA非洲裔活体捐献者， 纵向随访，以确定APOL 1风险变异体在高血压、CKD发展中的作用。 以及捐献后的终末期肾病（ESRD）。捐赠者和接受者都将接受纵向随访 三年，生物样本包括血液、尿液、粪便和活组织检查将被储存， 进行生物测定以鉴定导致或触发肾功能下降的二次损伤， 无论是捐赠者还是接受者将制定适当的协议和程序，包括建立 一个基于网络的电子数据采集工具，用于收集和跟踪研究参与者的数据， 确保数据和样本安全有效地传输到科学数据研究中心。