The H3Africa Kidney Disease Cohort Study

H3Africa 肾脏疾病队列研究

• 批准号: 8986048
• 负责人: Dwomoa Adu
• 金额: $ 60.31万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-25 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8986048
• 关键词: Affect; Africa; Africa South of the Sahara; African; African American; African Trypanosomiasis; Apolipoproteins; Basic Science; Biopsy; Blood; Case-Control Studies; Cessation of life; Chronic Disease; Chronic Hepatitis C; Chronic Kidney Failure; Clinical; Clinical Research; Cohort Studies; Country; DNA; Data; Development; Diabetes Mellitus; Dialysis procedure; Disease; Disease Progression; Drug Formulations; End stage renal failure; Ethiopia; Etiology; Focal Segmental Glomerulosclerosis; Funding; Genes; Genetic; Genetic Determinism; Genetic Predisposition to Disease; Ghana; Glomerulonephritis; HIV; Health; Hepatitis B; Hepatitis B Virus; Hepatitis C virus; Heredity; High Prevalence; Human; Hypertension; Incidence; Individual; Infection; Intervention Trial; Investigation; Joints; Kenya; Kidney; Kidney Diseases; Kidney Transplantation; Life; Malaria; Membranous Glomerulonephritis; Natural History; Nigeria; Not Hispanic or Latino; Outcome; Parasites; Participant; Pathogenesis; Pattern; Phenotype; Population; Prevention strategy; RNA; Renal glomerular disease; Reporting; Research; Research Infrastructure; Research Personnel; Resources; Risk; Risk Factors; Role; Sample Size; Science; Secondary to; Serum; Sickle Cell Anemia; Specimen; Susceptibility Gene; Teaching Hospitals; Therapeutic Intervention; Therapeutic Trials; Tissues; Translational Research; Trypanosoma; Trypanosomiasis; United States National Institutes of Health; Universities; Urine; Variant; Wit; Work; case control; design; effective therapy; gene environment interaction; genetic variant; high risk; innovation; insight; killings; lifetime risk; modifiable risk; new therapeutic target; novel; programs; prospective; public health relevance; repository; risk variant; screening; translational study; treatment strategy

 DESCRIPTION (provided by applicant): African Americans (AA) have a greater than three-fold higher lifetime risk of end stage renal disease (ESRD) as compared to non-Hispanic Whites (7.8% to 2.8%) secondary to a higher prevalence of both chronic kidney disease (CKD) and glomerulonephritides (GN). Recent studies suggest that Blacks living in Sub-Saharan Africa (SSA) (African Blacks) may have a similarly high predilection to kidney disease as do AA and that underlying this similarity in the two populations (American and African Blacks) may be common genetic predispositions to kidney disease; the most notable of which are the APOL1 kidney risk variants that encode for apolipoprotein L1. Circulating apolipoprotein L1 acts as a trypanolytic factor capable of killing trypanosome parasites in human serum and may be protective against trypanosomiasis ("African sleeping sickness") which is endemic in 36 African countries. It is estimated that more than three million AA and greater than 50 million African Blacks have CKD due to clinically defined nephropathies (from hypertension, diabetes mellitus, sickle disease, etc.) and GN. A significant fraction of these will progress to ESRD which is a harbinger of imminent death in the African setting due to the scarcity of dialysis or kidney transplantation. Building on our work in AA (Parsa A. N Eng J Med 2013;369(23):2183-960 & Lipkowitz MS. Kidney Int 2013;83(1):114-20) as well as in African Blacks (Science 2014;344(6190):1346-9 & Tayo BO. Int Urol Nephrol 2013;45(2)485-94), we herein propose to leverage the resources and expertise in the ongoing, NIH-funded, case-controlled H3Africa Kidney Disease Study to conduct a multinational prospective cohort study in 3,000 participants with clinically defined nephropathies and in 1,000 participants with biopsy-confirmed incident glomerular disease (for a total sample size of 4,000 HIV-negative African Blacks with kidney disease) to accomplish the following research objectives: (1) determine whether APOL1 risk variants independently predict kidney disease progression and identify modifiable risk factors for kidney disease progression in African Blacks; (2) elucidate the causative role of gene-environment interactions (APOL1-infections) and their joint and several effects on the outcomes of GN among African Blacks by country (n=4) and region (East vs. West Africa) and (3) establish a high quality resource (data and specimen repository of blood, urine, DNA, RNA and kidney tissue) for basic, clinical and translational research in kidney disease and other chronic diseases. The proposed study is innovative in that it is the first adequately powered prospective cohort study to both identify the genetic determinants and characterize the phenotype for kidney disease progression in SSA. The overall impact of the study is likely to be very high as it would: (i) yield new information relevant for the development of kidney disease screening programs, preventative strategies and therapeutic intervention trials and (ii) create a new platform essentia for basic, clinical and translational studies of kidney disease in all people of African ancestry. o wit, this unique research resource would be made readily accessible to researchers worldwide.