Biomarker-Based Diagnostic Algorithms To Prevent, Detect And Guide Treatment Of Kidney Disease In Persons Living With HIV

基于生物标志物的诊断算法，用于预防、检测和指导 HIV 感染者肾脏疾病的治疗

• 批准号: 10254848
• 负责人: Michelle M Estrella
• 金额: $ 79.94万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10254848
• 关键词: Abate; Acute; Address; Affect; Algorithms; Anti-Retroviral Agents; Bayesian Analysis; Benign; Biological Markers; Caring; Chronic; Chronic Kidney Failure; Clinical; Clinical Data; Cohort Studies; Computational algorithm; Creatinine; Data; Deterioration; Diagnosis; Diagnostic; Diagnostic tests; Dimensions; Early Diagnosis; Event; Face; Factor Analysis; Future; Goals; HIV; HIV Infections; Health; Individual; Inflammation; Influentials; Injury; Injury to Kidney; Intervention; Investigation; Kidney; Kidney Diseases; Maps; Measures; Mediating; Metabolic; Mission; Monitor; Morbidity - disease rate; Nephrons; Outcome; Patients; Pattern; Persons; Pharmaceutical Preparations; Phase; Population; Prevention; Prevention strategy; Preventive; Probability; Prognosis; Proteins; Renal function; Renal tubule structure; Research Personnel; Risk; Risk Factors; Safety; Serum; Severities; Site; Surrogate Markers; System; Tenofovir; Testing; The Multicenter AIDS Cohort Study; Time; Toxic effect; Tubular formation; Update; Urine; Viral; Women' s Interagency HIV Study; Work; aggressive therapy; base; biomarker panel; cardiovascular disorder risk; clinical care; clinical practice; clinical risk; clinical translation; cohort; comorbidity; diagnostic biomarker; disease diagnosis; experience; follow-up; functional decline; health assessment; hemodynamics; high risk; high risk population; improved; individualized prevention; modifiable risk; mortality; multidisciplinary; nephrotoxicity; novel marker; novel strategies; personalized predictions; prevent; prognostic; prognostic significance; renal damage; success; targeted treatment; tool; treatment response; treatment strategy; vascular risk factor

ABSTRACT Our strategies for preventing, detecting, and monitoring kidney disease in people living with HIV (PLWH) have lagged far behind the incredible advances in HIV treatment and management over the past decades. Despite their proven limitations for diagnosing chronic kidney disease (CKD), the serum creatinine and the urine protein concentration remain the mainstays of kidney health monitoring for PLWH. While clinical kidney diagnostic testing has stagnated, PLWH face an increasing myriad of insults to the kidneys, including metabolic and vascular risk factors, chronic inflammation, direct viral toxicity, and potentially nephrotoxic medications. Consequently, CKD has accelerated as a cause of morbidity and mortality in PLWH. Over the past decade, our pioneering work in PLWH has shown that biomarkers of tubule health yield significantly more diagnostic and prognostic information than could be obtained by conventional kidney health assessments. This competitive renewal application will build upon this prior work to fulfill our mission of fundamentally changing how kidney disease is detected, diagnosed and monitored. This proposal strategically addresses the most challenging aspects of CKD diagnosis and treatment, and will provide the evidence needed to advance kidney biomarker-based diagnostic algorithms into clinical practice. Successful completion and clinical translation of our Aims will allow clinicians to achieve the following major goals. 1) Among PLWH with acute elevations of the serum creatinine, we will be able to distinguish whether or not the individual has true kidney injury and to identify the patterns of injury that forecast the likelihood of kidney function recovering or worsening during subsequent follow-up (Aim 1). 2) For each modifiable kidney disease risk factor in PLWH, we will be able to monitor the impact of improvements and deteriorations in risk factor control on the kidney, using a tailored set of surrogate biomarkers (Aim 2a). 3) We will use a time- updated algorithm that will integrate dynamic changes in risk factors and kidney biomarkers to prognosticate longitudinal changes in risk for rapidly progressive kidney disease, for each individual PLWH (Aim 2b). 4) For the many PLWH with myriad exposures that threaten or lower risk for progressive kidney disease, we will utilize a novel biomarker-based monitoring algorithm to identify and prioritize each risk factor based on its Bayesian probability of causing the observed pattern and severity of kidney damage. Despite these ambitious goals, this proposal is both feasible and efficient as we will use biospecimens and clinical data that have been or will be collected among PLWH in the Multicenter AIDS Cohort Study (MACS), the Women’s Interagency HIV Study (WIHS), the MACS-WIHS Combined Cohort Study (MWCCS), and the Predictors of Acute Renal Injury Study (PARIS) cohorts. The study investigators are a multi-disciplinary team of experts who bring enormous enthusiasm, experience and commitment to the proposal and will guarantee its success.

抽象的 我们预防艾滋病毒（PLWH）患者预防，检测和监测肾脏疾病的策略 在过去的几十年中，远远落后于艾滋病毒治疗和管理的进步。 尽管它们对诊断性慢性肾脏疾病（CKD）的局限性有证实，血清肌酐和 尿液蛋白浓度仍然是PLWH肾脏健康监测的主要体系。而临床肾脏 诊断测试停滞不前，PLWH面临着越来越多的对孩子的侮辱，包括 代谢和血管危险因素，慢性炎症，直接病毒毒性以及潜在的肾毒性 药物。因此，CKD加速了PLWH中发病率和死亡率的原因。 在过去的十年中，我们在PLWH中的开创性工作表明，Tubele Health Harty的生物标志物 与常规肾脏健康相比，诊断和预后的信息要多得多 评估。这种竞争性更新申请将以这项先前的工作为基础，以履行我们的使命 基本上改变了检测，诊断和监测肾脏疾病的方式。这项提案从战略上 解决CKD诊断和治疗方面最挑战的方面，并将提供证据 需要将基于肾脏生物标志物的诊断算法推向临床实践。 我们目标的成功完成和临床翻译将使临床医生能够实现以下专业 目标。 1）在血清肌酐急性升高的PLWH中，我们将能够区分是否或 并非个人有真正的肾脏损伤，并确定了预测可能性的伤害模式 肾功能在随后的随访期间恢复或担心（AIM 1）。 2）对于每个可修改的肾脏 PLWH中的疾病风险因素，我们将能够监测改善和风险差异的影响 使用量身定制的替代生物标志物（AIM 2A）的肾脏控制因素控制。 3）我们将使用时间 - 更新的算法将整合风险因素和肾脏生物标志物的动态变化以证明 每种PLWH的纵向变化肾脏疾病风险的纵向变化（AIM 2B）。 4） 许多PLWH的无数暴露会威胁或降低发生性肾脏疾病的风险，我们将 利用一种新型的基于生物标志物的监测算法来识别和确定每个风险因素的优先级 贝叶斯引起观察到的肾脏损伤模式和严重程度的概率。尽管这些雄心勃勃 目标，该建议既可行又有效，因为我们将使用已经 或将在多中心艾滋病队列研究（MAC）的PLWH中收集在PLWH中 研究（WIHS），MACS-WIHS组合研究（MWCC）和急性肾脏损伤的预测因子 研究（巴黎）队列。研究调查人员是一个跨学科的专家团队，他们带来了巨大的 热情，经验和对提案的承诺，并将保证其成功。