Novel biomarkers of kidney injury in HIV-infected men

HIV感染者肾损伤的新生物标志物

• 批准号: 8783329
• 负责人: Vasantha Kolavennu Jotwani
• 金额: $ 7.7万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-03 至 2016-07-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8783329
• 关键词: Acquired Immunodeficiency Syndrome; Acute Renal Failure with Renal Papillary Necrosis; African American; Aging; Albuminuria; Anti-Retroviral Agents; Biological Markers; Caring; Caucasians; Caucasoid Race; Chronic Kidney Failure; Clinical; Cohort Studies; Creatinine; Detection; Development; Diabetes Mellitus; Diagnosis; Disease Progression; Drug toxicity; Early Diagnosis; Early identification; End stage renal failure; Enrollment; Epithelial Cells; Etiology; Exposure to; Fanconi Syndrome; Foundations; Functional disorder; Future; HIV; HIV Infections; HIV therapy; Health; Hepatitis C; Hypertension; Individual; Injury; Injury to Kidney; Interleukin-18; Intervention; Investigation; Kidney; Kidney Diseases; Kidney Function Tests; Measurement; Measures; Nephrons; Nephrotoxic; Participant; Pathology; Pattern; Persons; Pharmaceutical Preparations; Population; Proteinuria; Renal function; Research; Reverse Transcriptase Inhibitors; Risk Factors; Sampling; Serum; Site; Staging; Tenofovir; Therapeutic; Toxic effect; Tubular formation; Urine; Validation; Woman; antiretroviral therapy; base; clinical care; cohort; demographics; frontier; high risk; intravenous drug use; men; novel; novel marker; nucleotide analog; prevent; prognostic; public health relevance; rat KIM-1 protein; urinary

DESCRIPTION (provided by applicant): Despite advances in therapy, HIV-infected individuals remain at higher risk for kidney dysfunction than uninfected individuals. Current measures of kidney function, such as serum creatinine and dipstick proteinuria, are late and nonspecific markers of kidney damage in HIV-infected individuals, and do not differentiate the etiology or site of injury within the nephron. Early identification of tubular dysfunction is particularly important in HIV-infected persons receiving tenofovir, an antiretroviral medication with direct toxicity to proximal tubular epithelial cells. We propose a novel paradigm for the assessment of kidney health in HIV-infected individuals, using a panel of urinary biomarkers which can detect early kidney injury, localize pathology within the nephron, and differentiate drug toxicity from alternate etiologies of kidney damage. We recently measured urine levels of interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), a1-microglobulin (a1m), and albuminuria in 886 HIV-infected and 350 uninfected men enrolled in the Multicenter AIDS Cohort Study (MACS). The current project will compare levels of each biomarker between HIV-infected and uninfected men; identify the specific risk factors associated with each biomarker among the HIV-infected participants; determine the impact of tenofovir use on kidney health based on biomarker levels; and evaluate longitudinal associations of each urine biomarker with kidney function decline over 4 years. Identification of early kidney injury in HIV-infected persons, using biomarker levels, could enable targeted interventions prior to the development of irreversible kidney damage. Additionally, these research objectives will lay foundation for future longitudinal investigations examining the utilities of biomarkers for the detection of drug toxicity, particulary among HIV-infected persons receiving nephrotoxic therapies.

描述（由申请人提供）：尽管在治疗方面取得了进展，但HIV感染者仍然比未感染者有更高的肾功能障碍风险。目前肾功能的测量，如血清肌酐和试纸蛋白尿，是HIV感染者肾损伤的晚期和非特异性标志物，不能区分肾单位内的病因或损伤部位。肾小管功能障碍的早期识别在接受替诺福韦（一种对近端肾小管上皮细胞具有直接毒性的抗逆转录病毒药物）的HIV感染者中尤为重要。 我们提出了一种新的模式，用于评估HIV感染者的肾脏健康，使用一组尿液生物标志物，可以检测早期肾损伤，定位肾单位内的病理，并区分药物毒性和肾损伤的替代病因。我们最近在多中心艾滋病队列研究（MACS）中检测了886名HIV感染者和350名未感染者的尿液白细胞介素-18（IL-18）、肾损伤分子-1（KIM-1）、α 1-微球蛋白（α 1 m）和白蛋白尿水平。当前项目将比较艾滋病毒感染和未感染男性之间每种生物标志物的水平;确定艾滋病毒感染参与者中与每种生物标志物相关的特定风险因素;根据生物标志物水平确定替诺福韦的使用对肾脏健康的影响;并评估每种尿液生物标志物与4年内肾功能下降的纵向关联。 使用生物标志物水平识别艾滋病毒感染者的早期肾损伤，可以在不可逆肾损伤发生之前进行有针对性的干预。此外，这些研究目标将为未来的纵向调查奠定基础，检查生物标志物用于检测药物毒性的效用，特别是在接受肾毒性治疗的HIV感染者中。