Etiology of Persistent Microalbuminuria in Nigeria

尼日利亚持续性微量白蛋白尿的病因学

基本信息

批准号：
10325071
负责人：
Muktar Hassan Aliyu
金额：
$ 61.65万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10325071
关键词：
APOL1 gene Acquired Immunodeficiency Syndrome Address Adult Age Albumins Albuminuria Angiotensin Receptor Angiotensin-Converting Enzyme Inhibitors Bacterial Infections Biological Markers Blood Pressure CD14 gene CD4 Lymphocyte Count Cardiovascular Diseases Cardiovascular system Caring Cells Creatinine Cytomegalovirus Data Data Store Development Diabetes Mellitus Disease Early Diagnosis Endothelium Enrollment Etiology Exposure to Fibrin fragment D Filaria bancrofti Fumarates General Population HIV HIV Seronegativity HIV Seropositivity Hepatitis B Hepatitis C Hepatitis C co-infection High Prevalence Hypertension Inflammation Inflammatory Interleukin-6 Kidney Kidney Diseases Lead Lisinopril Loa loa Low Prevalence Measurement Medical Microalbuminuria Monitor Morbidity - disease rate Mycobacterium tuberculosis Nigeria Onchocerca volvulus Organ Parasitic infection Participant Persons Pharmaceutical Preparations Phase Plasmodium falciparum Population Prevalence Regimen Renin-Angiotensin-Aldosterone System Risk Risk Factors Risk Reduction Role Schistosoma Sickle Cell Trait Site Smoking Specimen Strongyloides stercoralis T-Cell Activation TNFR-Fc fusion protein TNFRSF1A gene Teaching Hospitals Tenofovir Testing Tuberculosis Viral Virus Diseases antiretroviral therapy cardiovascular risk factor cigarette smoking co-infection cohort comorbidity eligible participant endothelial dysfunction experience high risk immune activation inflammatory marker macroalbuminuria mortality nephrotoxicity non-diabetic normotensive prehypertension prospective randomized placebo controlled trial risk variant screening sex therapy development virology

项目摘要

ABSTRACT: Microalbuminuria is an independent risk factor for cardiovascular and kidney disease and a predictor of end organ damage, both in the general population and in persons living with HIV (PLWH). Microalbuminuria, defined as an albumin-to-creatinine ratio (uACR) 30-300 mg/g, can signify either early glomerular damage or microvascular endothelial dysfunction and has been used in the early detection of kidney disease. Microalbuminuria is also an important risk factor for mortality in PLWH treated with antiretroviral therapy (ART), likely as a marker for inflammation and endothelial activation. In the ongoing Renal Risk Reduction (R3) study in Nigeria, 36.9% had microalbuminuria confirmed by two measurements 4- 8 weeks apart, and 2.8% had macroalbuminuria (uACR >300 mg/g). The median duration on ART was 9 years [IQR 6,12], median CD4 cell count was 482 cells/mm3 [IQR 324–661], 95.7% were virally suppressed, and 12.7% had stage 1 or 2 hypertension (22.1% with pre-hypertension). In contrast, other traditional risk factors for albuminuria and kidney disease, including diabetes (2.1%), APOL1 high-risk genotype (6.2%), and smoking (5%) were uncommon. A significant proportion (~59%) were currently receiving potentially nephrotoxic ARV medications, specifically tenofovir disoproxil fumarate. Lastly, endemic co-infections, including viral (e.g. hepatitis B and C, Cytomegalovirus), parasitic (e.g. Plasmodium falciparum, Schistosoma species, Strongyloides stercoralis, Onchocerca volvulus, Loa loa, Wuchereria bancrofti), and bacterial (Mycobacterium tuberculosis) co-infections, may be potential contributors to albuminuria. To better understand this, we plan to test the following overarching hypothesis: Hypertension, immune activation from co-infections, and cumulative, long-term exposure to potentially nephrotoxic ARV medications contribute to the high rates of microalbuminuria in these ART-experienced adults. To test this hypothesis, we propose the following Specific Aims: 1) To compare the prevalence of albuminuria and established kidney disease risk factors in a large cohort of PLWH to age- and sex-matched HIV-negative adults presenting for routine medical care at the Aminu Kano Teaching Hospital in Kano, Nigeria. We will leverage data and stored specimens from 2500 R3 participants who were previously screened for microalbuminuria and will prospectively enroll an additional 300 PLWH recently initiated on ART (≤ 12 months) and 750 age- and sex-matched HIV-negative adults. 2) To determine the role that hypertension and other comorbid medical conditions (e.g. sickle cell trait or disease, immune activation/inflammation from parasitic infestations and tuberculosis, and exposure to potentially nephrotoxic ARV medications), have on the risk for development of albuminuria. We will enroll 1000 HIV-positive, ART-treated normoalbuminuric adults and 500 HIV-negative normoalbuminuric adults from Aim 1 and follow them longitudinally for three years.

摘要：微量白蛋白尿是心血管和肾脏疾病的独立危险因素，最终器官损伤的预测指标，包括普通人群和艾滋病毒（PLWH）的人。微量白蛋白尿，被定义为相册与造丁氨酸比率（UACR）30-300 mg/g，可以提早表示任何一个肾小球损伤或微血管内皮功能障碍，已用于早期检测肾脏疾病。微量白蛋白尿也是PLWH处理中死亡率的重要危险因素抗逆转录病毒疗法（ART），可能是炎症和内皮激活的标志物。在正在进行中尼日利亚的肾脏风险降低（R3）研究，有36.9％的微量白蛋白尿，通过两种测量值确认4-- 相距8周，2.8％的大藻尿症（UACR> 300 mg/g）。艺术的中间时间为9年 [IQR 6,12]，中位CD4细胞计数为482个细胞/mm3 [IQR 324–661]，实际上抑制了95.7％，而95.7％被抑制，并且 12.7％的患者患有1或2期高血压（催眠前22.1％）。相反，其他传统风险因素用于蛋白尿和肾脏疾病，包括糖尿病（2.1％），APOL1高风险基因型（6.2％）和吸烟（5％）并不常见。目前有显着比例（〜59％）正在接受潜在的肾毒性ARV 药物，特别是替诺福韦毒素。最后，内在共感染，包括病毒（例如肝炎B和C，巨细胞病毒），寄生虫（例如恶性疟原虫，血吸虫种类，血吸虫， Strongyloides stercoralis，onChocerca volvulus，loa loa，wuchereria bancrofti）和细菌（分枝杆菌结核病）共感染，可能是蛋白尿的潜在贡献者。为了更好地理解这一点，我们计划测试以下基本假设：高血压，来自共同感染的免疫激活以及累积，长期接触潜在的肾毒性ARV药物有助于高这些具有艺术经验的成年人的微量白蛋白尿症的发生率。为了检验这一假设，我们提出了遵循特定目的： 1）比较大量队列中蛋白尿的患病率和建立的肾脏疾病风险因素 PLWH到年龄和性别匹配的HIV阴性成年人，在Aminu举行常规医疗服务尼日利亚卡诺的卡诺教学医院。我们将利用2500 R3的数据并存储标本以前被筛选的微珠尿症的参与者，可能会添加额外 300 PLWH最近在ART（≤12个月）和750年龄和性别匹配的HIV阴性成年人开始。 2）确定高血压和其他合并症的作用（例如，镰状细胞性状或疾病，寄生虫侵染和结核病的免疫激活/炎症，并暴露于潜在的肾毒性ARV药物），有蛋白尿发展的风险。我们将注册 1000名HIV阳性，艺术治疗的正常珠尿素成年人和500个HIV阴性正常白蛋白酶成年人从AIM 1开始，并纵向跟随他们三年。