1/13 ApoL1 Genotypes in Kidney Donors and Long-Term Outcomes in Kidney Transplant Recipients Clinical Center

1/13 肾脏捐献者的 ApoL1 基因型和肾移植受者的长期结果 临床中心

• 批准号: 9975172
• 负责人: ALESSIA FORNONI
• 金额: $ 13.33万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 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/9975172
• 关键词: APOL1 gene; Address; Affect; African; African American; African Caribbean; Alleles; Allografting; Biological; Biology; Categories; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Sciences; Code; Collaborations; Communities; Data; Development; Disease; Enrollment; Ethnic Origin; Ethnic group; Evaluation; Florida; Funding; Genes; Genetic; Genetic study; Genotype; Graft Survival; Grant; Health; Hispanics; Human; Hypertension; Incidence; Individual; Infrastructure; Institutes; Kidney; Kidney Diseases; Kidney Failure; Kidney Transplantation; Knowledge; Latino; Link; Living Donors; Longitudinal cohort; Microalbuminuria; Molecular Profiling; Monitor; Network-based; Organ; Organ Donations; Organ Procurements; Organ Transplantation; Outcome; Patients; Population; Population Heterogeneity; Prevalence; Primates; Prospective Studies; Prospective cohort; Prospective cohort study; Proteinuria; Puerto Rico; Quality of life; Recovery; Renal function; Reperfusion Therapy; Reporting; Retrospective Studies; Risk; Sampling; Site; Southeastern United States; System; Translational Research; Transplant Recipients; Transplantation; United Network for Organ Sharing; United States; United States National Institutes of Health; United States Virgin Islands; Urine; Variant; Waiting Lists; allograft rejection; base; clinical center; cohort; design; follow-up; genetic variant; indexing; kidney biopsy; patient population; patient subsets; podocyte; repository; risk variant; social media; tool; transplant centers

ABSTRACT The kidney donor profile index (KDPI) incorporates factors known to affect allograft survival; among them, African ethnicity is a variable considered to adversely affect graft outcome. Risk variants of Apoliproprotein L1 (APOL1) gene have been recently linked to chronic kidney disease in individuals of African ancestry. Retrospective data suggest that the presence of two APOL1 risk variants in the donor can affect long-term allograft outcomes. These data will need to be validated in prospective cohorts and studied in donors of African ancestry, including the unique population of Latinos of African Descent which will be captured by our network design (Florida/Puerto Rico/US Virgin Islands). Aim 1 of this application will validate long-term graft outcomes in recipients of organs from deceased and living donors of African descent carrying two APOL1 risk variants when compared to less than two risk variants. Aim 2 will compare recipient outcomes between Latinos of African Descent and Blacks (African Americans and African Caribbeans) as well as capture potential interactions with donor-, recipient- and transplant-related “second hits”. Aim 3 will focus on the clinical consequences of donation from individuals carrying two APOL1 risk variants and will develop translational tools for the study of ApoL1 biology to be shared with the APOLLO Network and with the scientific community. We have engaged a unique team of interdisciplinary and interinstitutional collaborators which includes five Organ Procurement Recovery Agencies as well as eight transplant centers serving Florida, Puerto Rico and the US Virgin Islands along with UNOS support. In addition, we are collaborating with geneticists funded by a NIH-U54 grant focused on genetic studies in diverse patient populations. To leverage our expertise, we have engaged world renowned experts in the field of ApoL1 biology/genetics as well as our Clinical and Translational Science Institute. These relationships along with our previous expertise in large multi-center longitudinal cohorts, such as NEPTUNE and CureGN, will aid in the successful development of this study at a national level.

摘要