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: 8958708
• 负责人: Vasantha Kolavennu Jotwani
• 金额: $ 8.02万
• 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/8958708
• 关键词: Acquired Immunodeficiency Syndrome; Acute Renal Failure with Renal Papillary Necrosis; African American; Aging; Albuminuria; Anti-Retroviral Agents; Biological Markers; Caring; Caucasians; 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)：尽管治疗取得了进步，但艾滋病毒感染者患肾功能障碍的风险仍然高于未感染者。目前的肾功能指标，如血清肌酐和试纸蛋白尿，是HIV感染者肾脏损害的迟发和非特异性标志物，并且没有区分肾单位内损害的病因或部位。对于接受替诺福韦治疗的HIV感染者来说，及早发现肾小管功能障碍尤为重要。替诺福韦是一种对近端肾小管上皮细胞有直接毒性的抗逆转录病毒药物。我们提出了一种评估HIV感染者肾脏健康的新范式，使用一组尿液生物标志物可以检测早期肾脏损伤，定位肾单位内的病理，并区分药物毒性和肾脏损害的替代病因。我们最近检测了参加多中心艾滋病队列研究(MACS)的886名HIV感染者和350名非感染者的尿液中白介素18(IL-18)、肾脏损伤分子-1(KIM-1)、A1-微球蛋白(A1M)和蛋白尿的水平。目前的项目将比较艾滋病毒感染者和未感染者之间每个生物标志物的水平；在艾滋病毒感染者中确定与每个生物标志物相关的具体风险因素；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；并评估每个尿液生物标志物与肾功能在4年内下降的纵向关联。使用生物标记物水平识别艾滋病毒感染者的早期肾脏损伤，可以在发生不可逆转的肾脏损伤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，检查生物标记物在检测药物毒性方面的作用，特别是在接受肾毒性治疗的艾滋病毒感染者中。