Biomarkers of Immune Activation in African Americans with CKD

患有 CKD 的非裔美国人免疫激活的生物标志物

• 批准号: 10686752
• 负责人: Teresa Chen
• 金额: $ 13.35万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10686752
• 关键词: APOL1 gene; Adaptive Immune System; Affect; African American; African American population; African ancestry; American; Amlodipine; Applications Grants; Atherosclerosis Risk in Communities; Award; Biological Markers; Biology; Blood Pressure; Chronic Kidney Failure; Chronic Kidney Insufficiency; Clinical; Complex; Data; Data Analyses; Data Store; Development; Dietary Factors; Dietary Potassium; Dietary Sodium; Disease Progression; Doctor of Philosophy; End stage renal failure; Endothelial Cells; Ensure; Environment; Epidemiology; European; Experimental Models; Funding Mechanisms; Future; General Population; Genotype; Goals; High Prevalence; Hour; Human body; Hypertension; Immune; Immunologic Markers; In Vitro; Individual; Intake; Interferon Type II; Intervention; Invaded; Investigation; K-Series Research Career Programs; Kidney Diseases; Letters; Link; Measurement; Measures; Mentors; Mentorship; Methods; Metoprolol; Molecular Epidemiology; Nephrology; Outcome; Oxidative Stress; Pathway interactions; Pharmaceutical Preparations; Phase; Populations at Risk; Potassium; Ramipril; Randomized; Renal function; Reproducibility; Research; Research Design; Research Personnel; Research Project Grants; Resources; Risk; Risk Factors; Role; Sampling; Scientist; Serum; Sodium; Sodium Chloride; System; TNF gene; Time; Training; Tryptophan Metabolism Pathway; Tumor Necrosis Factor Activation; Tumor Necrosis Factor Receptor; United States National Institutes of Health; Universities; Urine; Visit; Water; blood pressure control; blood pressure intervention; blood pressure medication; career; cohort; demographics; diabetic patient; endothelial dysfunction; experience; fatty acid oxidation; follow-up; genetic epidemiology; genetic risk factor; high risk; immune activation; improved; insight; medical schools; metabolomics; microorganism; non-diabetic; novel; podocyte; predictive marker; professor; randomized trial; receptor; risk variant; skills; treatment arm; trial design

PROJECT SUMMARY/ABSTRACT Teresa K. Chen, MD, MHS is an Assistant Professor in the Division of Nephrology at Johns Hopkins University School of Medicine. She is applying for a K08 Mentored Clinical Scientist Research Career Development Award in order to acquire the necessary skills and mentored research experience to become an independent investigator in the field of chronic kidney disease (CKD). The proposed 5-year plan includes advanced coursework in epidemiology; practical experience in the measurement of biomarkers; and mentorship by an extraordinarily experienced, committed and diverse mentorship team [co-primary mentors, Lawrence Appel, MD, MPH and Morgan Grams, MD, PhD; co-mentor, Michelle Estrella, MD, MHS]. With resources provided by this award, Dr. Chen will develop proficiencies in study design, genetic and molecular epidemiology, and longitudinal data analysis related to CKD. Her proposed research project focuses on the role of immune activation in CKD progression and the interactive effects of immune activation with APOL1 risk variants. African Americans are disproportionately affected by CKD. This is in part due to the higher prevalence of APOL1 risk variants, genetic risk factors for kidney disease among individuals of African ancestry. The role of immune activation in the progression of non-diabetic CKD, particularly in APOL1 high-risk individuals, is unclear. The objectives of the proposed research are to: 1) study the associations of biomarkers of immune activation with CKD progression among non-diabetic African Americans with CKD attributed to hypertension; 2) determine whether the APOL1-associated risk for CKD progression is augmented by immune activation; 3) assess whether blood pressure interventions and dietary factors are associated with longitudinal changes in biomarkers of immune activation; 4) identify metabolomic predictors of biomarkers of immune activation. With over 10 years of follow-up, rigorously collected data, and stored biospecimens, the African American Study of Kidney Disease and Hypertension (AASK) represents an ideal cohort in which to study these potential associations. APOL1 genotyping and metabolomics measurements have previously been completed in AASK through other NIH-funded mechanisms. We propose to use stored serum samples from the baseline and 12- month visits of the trial phase to measure the following biomarkers of immune activation: tumor necrosis factor alpha (TNF-α), soluble TNF receptors 1 and 2 (sTNFR1 and sTNFR2), and interferon gamma (IFN-γ). The results of the proposed study will clarify the role of immune activation in CKD progression and perhaps identify novel targets for intervention. This could have important clinical implications in the treatment of African Americans with non-diabetic CKD, particularly among those with the APOL1 risk variants. The proposed research will also support Dr. Chen's long term-goal of transitioning towards an independent research career that ultimately improves the management and outcomes of African Americans with CKD. The rich training environment of Johns Hopkins University will ensure that she achieves these goals.

项目摘要/摘要 MHS医学博士Teresa K. Chen是约翰·霍普金斯大学肾脏科学系的助理教授 医学院。她正在申请K08指导的临床科学家研究职业发展 奖励以获得必要的技能并改善研究经验，以成为独立的技能 慢性肾脏病（CKD）领域的研究者。拟议的5年计划包括高级 流行病学课程；在测量生物标志物方面的实践经验；和一个由 经验丰富，承诺和潜水员的心态团队[联合促进心态，劳伦斯·阿佩尔（Lawrence Appel）， MD，MPH和Morgan Grams，医学博士，博士；米歇尔·埃斯特雷拉（Michelle Estrella），医学博士，MHS]。提供资源由 该奖项将在研究设计，遗传和分子流行病学以及 纵向数据分析与CKD有关。她提出的研究项目的重点是免疫的作用 CKD进程的激活以及与Apol1风险变体免疫激活的相互作用。 非裔美国人受到CKD的影响不成比例。这部分是由于较高的患病率 APOL1风险变异，非洲血统个体中肾脏疾病的遗传危险因素。的作用 非糖尿病CKD进展的免疫激活，特别是在Apol1高危个体中，是 不清楚。拟议研究的目标是：1）研究免疫的生物标志物的关联 CKD的非糖尿病非裔美国人中CKD进展的激活归因于高血压； 2） 确定免疫激活是否会增加与APOL1相关的CKD进展风险； 3） 评估血压干预和饮食因素是否与纵向变化有关 免疫激活的生物标志物； 4）确定免疫激活生物标志物的代谢组预测因子。和 在非洲裔美国人的研究中，超过10年的随访，严格收集的数据和存储的生物测量研究 肾脏疾病和高血压（AASK）代表了研究这些潜力的理想人群 协会。 APOL1基因分型和代谢组学测量以前已在AASK中完成 通过其他NIH资助的机制。我们建议使用基线和12-- 试验阶段的月份访问以测量以下免疫激活生物标志物：肿瘤坏死因子 alpha（TNF-α），可溶性TNF受体1和2（STNFR1和STNFR2）以及干扰素伽马（IFN-γ）。 拟议研究的结果将阐明免疫激活在CKD进展中的作用，甚至可能 确定新的干预目标。这可能对非洲的治疗具有重要的临床意义 患有非糖尿病CKD的美国人，尤其是在具有APOL1风险变体的美国人中。提议 研究还将支持陈博士对独立研究职业过渡的长期目标 最终，通过CKD改善了非洲裔美国人的管理和结果。丰富的培训 约翰霍普金斯大学的环境将确保她实现这些目标。