U Maryland Mid-Atlantic APOLLO Research Network Omic and Clinical Center

马里兰大学大西洋中部阿波罗研究网络组学和临床中心

基本信息

批准号：
10729890
负责人：
Jonathan S Bromberg
金额：
$ 19.95万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-25 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10729890
关键词：
Acceleration Acute Address African American African ancestry Albumins Allografting American Antibodies Apolipoproteins Bacterial Infections Biopsy Blood Child Classification Clinical Data Consent Cost Savings Counseling Creatinine DNA Data Disparity Donor person Education Enrollment Ensure Environmental Risk Factor European Evaluation Face Failure Genes Genetic Genotype Geography Graft Survival HLA Antigens Health Care Costs Hospitals Immunosuppression Individual Kidney Kidney Failure Kidney Transplantation Lesion Living Donors Longterm Follow-up Maryland Measures Medical Medical center Monitor Organ Outcome Outcome Study Outcomes Research Participant Pattern Phase Phenotype Policies Prevalence Proteinuria Quality of life Recurrent disease Registries Renal function Reporting Research Research Personnel Risk Role Safety Serum Site Slide Time Transplant Recipients Transplantation United Network for Organ Sharing United States National Institutes of Health Universities Urine Variant Virus Diseases Washington biobank clinical center cohort digital pathology ethnic difference follow-up gene interaction genetic risk factor graft failure high risk improved indexing kidney biopsy living kidney donor medical schools novel post-transplant primary outcome programs prospective racial difference recruit repository risk variant safety assessment secondary outcome

项目摘要

Project Summary Relative to kidneys from European American (EA) deceased donors (DDs), kidneys transplanted from African American (AA) DDs have significantly shorter graft survival. Several landmark studies revealed kidney transplants from DDs with two apolipoprotein L1 gene (APOL1) risk variants, defining APOL1 high-risk genotypes, have shorter graft survival. APOL1-associated lesions were detected in most failed grafts from these APOL1 high-risk genotype DDs. Importantly, many kidneys transplanted from DDs with two APOL1 risk variants do not fail rapidly. We hypothesize that APOL1 interacts with other environmental and inherited factors to cause early failure of DD kidney transplants (DDKT). The National Institutes of Health (NIH) established the “APOL1 Long-term Kidney Transplantation Outcomes” (APOLLO) U01 Consortium in 2017 to prospectively address several critical questions regarding broad APOL1 genotyping in AA DDKT and assessing safety in AA live kidney donation. Results could transform the US policy for allocation of kidneys and lead to improved graft survival, reassignment of AA DD kidneys to lower (i.e., better) kidney donor profile index (KDPI) classification and thus lesser discard of good-quality kidneys and more kidney transplants, greater assurance of safety for living AA donors, and cost savings. In addition, the role of recipient APOL1 genotypes on transplant outcomes is controversial and APOLLO addresses this question. The APOLLO Consortium includes a Scientific and Data Research Center (SDRC) and 13 Clinical Centers (CCs), including our center. Our CC, the “10/14 APOL1 Long- term Kidney Transplantation Outcomes Network (APOLLO) Clinical Center” at the University of Maryland School of Medicine (UMSOM) and Medical Center (UMMC) is comprised of 4 additional kidney transplant programs at the Sentara, Georgetown, George Washington, and Children’s National Hospitals. We recruited recipients of AA DD and LD kidney transplants and AA live donors during the initial phase of APOLLO. Through 9/29/22, the APOLLO SDRC and Consortium have prospectively collected DNA from a national cohort of 3604 AA DDs and are following outcomes in 4890 DDKT. The 13 APOLLO CCs consented and collected bio-samples from 2436 DDKT recipients. In APOLLO Phase 1, our University of Maryland CC enrolled 65.3% of all recipients of an APOLLO DDKT with DNA and biosamples (81 out of 124). We also recruited 32 AA LD and 28 AA LDKT recipients. In APOLLO Phase 2, the Specific Aims of our CC are to: Aim 1. To prospectively collect long-term follow-up data on all APOLLO participants. Aim 2. To provide detailed clinical data and biospecimens on APOLLO participants from our CC. Aim 3. To facilitate return of APOL1 genotype results. Impact: APOL1 genotyping has the potential to reduce the discard of good-quality kidneys from AA donors and increase the number of transplants overall. Identifying the secondary environmental or genetic factors that modify phenotypic outcomes will improve allograft survival and quality of life for all transplant recipients.

项目摘要相对于来自欧美（EA）已故捐赠者（DDS）的孩子，Kidsneys从非裔美国人（AA）DDS的移植物生存较短。一些具有里程碑意义的研究揭示了肾脏来自DDS具有两个载脂蛋白L1基因（APOL1）风险变体的DDS的移植，定义Apol1高风险基因型，具有较短的移植物存活率。在这些失败的移植物中检测到与Apol1相关的病变 APOL1高风险基因型DDS。重要的是，许多从DDS移植的儿童具有两个Apol1风险变体不要迅速失败。我们假设Apol1与其他环境和继承因素相互作用，以引起 DD肾脏移植的早期失败（DDKT）。美国国立卫生研究院（NIH）建立了“ Apol1 长期肾脏移植成果”（Apollo）U01联盟2017年前瞻性地解决关于AA DDKT中广泛的APOL1基因分型的几个关键问题，并评估AA活肾脏的安全性捐款。结果可能会改变美国对肾脏分配的政策，并导致移植物生存的提高，将AA DD Kidsneys重新分配到较低（即更好的）肾脏捐赠者概况指数（KDPI）分类，因此较少丢弃优质孩子和更多的肾脏移植，对生活的安全性更大捐助者和节省成本。此外，受体Apol1基因型在移植结果中的作用是有争议的和阿波罗解决了这个问题。阿波罗财团包括科学和数据研究中心（SDRC）和13个临床中心（CCS），包括我们的中心。我们的CC，“ 10/14 apol1长马里兰大学学校的术语肾脏移植成果网络（阿波罗）临床中心” 医学（UMSOM）和医疗中心（UMMC）由4个其他肾脏移植程序组成 Sentara，Georgetown，George Washington和儿童国家医院。我们招募了AA的接收者 DD和LD肾脏移植和AA的活捐赠者在阿波罗的初期。到9/29/22， Apollo SDRC和财团已将DNA从3604 AA DDS的全国队列和在4890 DDKT中以下结果。 13个阿波罗CCS同意并收集了2436年的生物样本 DDKT收件人。在阿波罗第一阶段，我们的马里兰州大学CC招收了65.3％带有DNA和生物样本的Apollo DDKT（124中的81个）。我们还招募了32 AA LD和28 AA LDKT 收件人。在阿波罗第2阶段，我们CC的具体目的是：目标1。所有阿波罗参与者的后续数据。目的2。为提供详细的临床数据和生物测量我们CC的Apollo参与者。目标3。促进apol1基因型结果的返回。影响：apol1 基因分型有可能减少AA捐助者的优质孩子的丢弃并增加总体移植数量。识别改变表型的次要环境或遗传因素结果将改善所有移植受者的同种异体移植生存和生活质量。