Etiology of Persistent Microalbuminuria in Nigeria

尼日利亚持续性微量白蛋白尿的病因学

• 批准号: 10617771
• 负责人: Muktar Hassan Aliyu
• 金额: $ 52.69万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 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/10617771
• 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; 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; 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; 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; vascular endothelial dysfunction

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