The H3Africa Kidney Disease Cohort Study

H3Africa 肾脏疾病队列研究

• 批准号: 9148192
• 负责人: Dwomoa Adu
• 金额: $ 58.41万
• 依托单位: UNIVERSITY OF ARIZONA
• 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 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9148192
• 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; End stage renal failure; Ethiopia; Etiology; Focal Segmental Glomerulosclerosis; Formulation; 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; 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.

 描述（由申请方提供）：与非西班牙裔白人（7.8%至2.8%）相比，非洲裔美国人（AA）的终末期肾病（ESRD）终身风险高出3倍以上，继发于慢性肾病（CKD）和肾小球肾炎（GN）的患病率较高。最近的研究表明，生活在撒哈拉以南非洲（SSA）的黑人（非洲黑人）可能与AA一样对肾脏疾病具有相似的高偏好，并且在两个人群（美国和非洲黑人）中的这种相似性可能是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APOL 1肾脏风险变体。循环载脂蛋白L1作为一种锥虫分解因子，能够杀死人血清中的锥虫寄生虫，并可能对36个非洲国家流行的锥虫病（“非洲昏睡病”）具有保护作用。据估计，超过300万AA和超过5000万非洲黑人由于临床定义的肾病（来自高血压、糖尿病、镰状病等）而患有CKD。的GN。其中很大一部分将进展为终末期肾病，这是非洲环境中由于缺乏透析或肾移植而即将死亡的预兆。基于我们在AA（Parsa A. N Eng J Med 2013;369（23）：2183-960 & Lipkowitz MS. Kidney Int 2013;83（1）：114-20）以及非洲黑人（Science 2014;344（6190）：1346-9 & Tayo BO.国际泌尿学和肾病学2013年; 45（2）485-94），我们在此建议利用正在进行的NIH资助的病例对照H3非洲肾病研究的资源和专业知识，在3，000名患有临床定义肾病的参与者和1，000名患有活检证实的偶发肾小球疾病的参与者中进行多国前瞻性队列研究（总样本量为4，000名患有肾脏疾病的HIV阴性非洲黑人），以实现以下研究目标：（1）确定APOL 1风险变体是否独立预测肾脏疾病进展，并确定非洲黑人肾脏疾病进展的可改变风险因素;（2）阐明基因-环境相互作用的成因作用（APOL 1-感染）及其对非洲黑人GN结局的联合和多重影响，按国家（n=4）和地区列出（3）建立高质量的资源（血液、尿液、DNA、RNA和肾脏组织的数据和标本库），用于肾脏疾病和其他慢性病的基础、临床和转化研究。拟议的研究是创新的，因为它是第一个充分把握度的前瞻性队列研究，既确定了遗传决定因素，又表征了SSA中肾脏疾病进展的表型。该研究的总体影响可能非常高，因为它将：（i）产生与肾脏疾病筛查计划，预防策略和治疗干预试验开发相关的新信息，（ii）为所有非洲血统人群的肾脏疾病基础，临床和转化研究创造一个新的平台。也就是说，这一独特的研究资源将随时提供给世界各地的研究人员。