The H3Africa Kidney Disease Cohort Study

H3Africa 肾脏疾病队列研究

• 批准号: 10001248
• 负责人: Dwomoa Adu
• 金额: $ 59.41万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10001248
• 关键词: Affect; Africa; Africa South of the Sahara; African; African American; African Trypanosomiasis; American; Apolipoproteins; Basic Science; Biopsy; Blood; Case-Control Studies; Cessation of life; Chronic Disease; Chronic Hepatitis C; Chronic Kidney Failure; Clinical; Clinical Research; Cohort Studies; Controlled Study; Country; DNA; Data; Diabetes Mellitus; Dialysis procedure; Disease; Disease Progression; End stage renal failure; Ethiopia; Etiology; Focal Segmental Glomerulosclerosis; Formulation; Funding; Genes; Genetic; Genetic Determinism; Genetic Predisposition to Disease; Ghana; HIV Seronegativity; 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; Longitudinal cohort study; Malaria; Membranous Glomerulonephritis; Natural History; Nigeria; Not Hispanic or Latino; Outcome; Parasites; Participant; Pathogenesis; Pattern; Phenotype; Population; Prevention strategy; Prospective cohort study; 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; design; effective therapy; gene environment interaction; genetic variant; high risk; infection risk; innovation; insight; kidney biopsy; lifetime risk; modifiable risk; nephrogenesis; new therapeutic target; novel; public health relevance; repository; research study; risk variant; screening; screening program; 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.

 描述（由适用提供）：与非西班牙裔白人（7.8％至2.8％）相比，非洲裔美国人（AA）的终身阶段肾病（ESRD）的终生风险高三倍，其继发于慢性肾脏病（CKD）和Glomerulullullulonephritides（GN）的患病率高（7.8％至2.8％）。最近的研究表明，居住在撒哈拉以南非洲（SSA）（非洲黑人）的黑人可能对肾脏疾病的预测可能与AA一样高，并且在两个人群（美国和非洲黑人）中的这种相似性可能是对肾脏疾病的常见遗传易感性。其中最值得注意的是编码载脂蛋白L1的Apol1肾脏风险变体。 Circulating apolipoprotein L1 acts as a trypanolytic factor capable of killing trypanosome parasites in human serum and may be protected against trypanosamiasis ("African sleeping sickness") 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。其中很大一部分将进展到ESRD，这是由于透析或肾脏移植的稀缺而在非洲情况下即将死亡的预兆。以我们在AA（PARSA）A。N Eng J Med 2013; 369（23）的工作为基础。2183-960＆Lipkowitz MS。肾脏INT 2013; 83（1）：114-20）以及非洲黑人（Science 2014; 344; 344（6190）：1346-9＆TayoBo。IntUrol Nephrol 2013; 45（2）485-94），我们在这里提出了在启用的，NIH-FUNDERN的疾病中，我们在这里提出了启用的资源和专业知识，在3,000名患有临床定义的肾病的参与者中，有1,000名活检确认事件入射肾小球疾病的参与者中的跨国前瞻性队列研究（对于4,000名HIV-NIV非洲黑人黑人患有肾脏疾病的总体样本量），以实现以下研究目标：（1）确定APOL1风险疾病的进度，并确定对肾上腺疾病的疾病进度，并确定型号型号的培训，并确定了适用于培养的型号，并确定了型号的培训，并确定了适用于培养的型号，并确定了适用于培养的疾病，并确定了适用于培养的疾病，并确定了适用于培养的疾病，并确定了适用于培养的疾病，并确定了型号的培养; （2）阐明基因环境相互作用（APOL1 - 发现）的真正作用及其联合以及对非洲黑人（n = 4）和地区（东非）和地区（东非）和（3）高质量资源（数据和标本的血液，尿液，尿液，RNA和肾小球的基本疾病）的高质量资源（n = 4）和地区（East vs. West非洲）和地区（East vs. 3）对GN的结果的几种影响疾病。拟议的研究具有创新性，因为它是第一个识别遗传决定剂并表征SSA肾脏疾病进展的表型的首次适当动力的前瞻性队列研究。这项研究的总体影响可能很高：（i）产生与肾脏疾病筛查计划，预防性策略和治疗干预试验相关的新信息，并且（ii）为非洲祖先的所有人群肾脏疾病的基本，临床和翻译研究创造了一个新的平台。机智，这个独特的研究资源将在全球研究人员容易获得。