A Triple Marker Approach To Optimize CKD Detection Among Black and White Adults

描述(申请人提供)：慢性肾病(CKD)是一种高度病态的疾病，它对种族/少数民族的影响不成比例。早期发现和治疗是预防流行病学的基石。然而，到目前为止，在没有糖尿病的人中进行CKD筛查还没有达成共识。在非糖尿病患者中，目前的临床策略依赖于血清肌酐来诊断CKD，而这一策略遗漏了许多高危人群。事实上，在美国，每6个成年人中就有1个可能患有未被发现的CKD，尽管测量了肌酐。血清肌酐因年龄和种族而有偏差，这导致不能可靠地检测出跨年龄和种族/民族的慢性肾脏病。尽管已有已建立的肾脏损伤标志物，如白蛋白/肌酐比率(ACR)和另一种滤过标志物，胱抑素C，但在一般临床实践中，这些指标并不被常规推荐或使用。这些标记物已被证明可以改善CKD风险分层，但它们在CKD筛查中的作用尚不清楚。在高达16%的美国成年人中，ACR和胱抑素C可以检测到肌酐遗漏的CKD(隐匿性CKD)。患有隐匿性CKD的人死亡、心血管事件和进展为终末期肾病的风险很高。使用肌酐、胱抑素C和ACR的三重标记物方法来检测CKD还没有研究。此外，缺乏证据来确定谁将从CKD筛查中受益最大，这阻碍了对有针对性的筛查计划的调查。如果没有有效的筛查计划，我们发现CKD以及设计和评估预防策略的能力是有限的。这一应用提出了CKD预防领域的范式转变，通过开发必要的知识来设计、评估和实施跨不同人群的有效CKD筛查策略。具体地说，我们建议从四个大型的、持续的、由NIH资助的队列中收集数据，这些队列代表了超过27,000名年龄在28-84岁的黑人和白人：青年冠状动脉风险发展(CARDIA)、动脉粥样硬化的多种族研究(MESA)、中风的地理和种族差异的原因(CONTS)以及健康、老龄化和身体成分(Health ABC)研究。我们建议使用这些汇集的数据来实施三重标记物方法来调查非糖尿病患者中隐匿性CKD的患病率。我们将评估通过Cystatin C或ACR进行筛查以检测隐匿性CKD所需的数量。我们的第二个目标是全面评估与隐匿性CKD相关的危险因素，并按年龄、性别和种族/民族进行评估。然后，我们将开发一个隐匿性CKD的预测工具和一个临床医生友好的在线计算器，以估计个人患隐匿性CKD的概率。这些项目产生的数据可以直接导致评估针对个人风险的筛查战略。

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) is highly morbid, and it affects race/ethnic minorities disproportionately. Early detection and treatment are the cornerstones of prevention epidemiology. Yet to date, there is no consensus for CKD screening among persons without diabetes. The current clinical strategy among non-diabetics relies on serum creatinine for diagnosing CKD, and this strategy misses many persons at risk. In fact, 1 in 6 adults in the U.S. may have undetected CKD despite having creatinine measured. Serum creatinine is biased by age and race, which results in the inability to reliably detect CKD across age and race/ethnic groups. Despite the availability of an established marker of kidney injury such as albumin-to-creatinine ratio (ACR) and an alternative filtration marker, cystatin C, these are not routinely recommended or used in general clinical practice. These markers have been shown to improve CKD risk stratification, but their utility in CKD screening is not known. ACR and cystatin C can detect CKD that is missed by creatinine (occult CKD) in up to 16% of U.S. adults. Persons with occult CKD are at high risk for death, cardiovascular events and progression to ESRD. The use of a triple marker approach of creatinine, cystatin C, and ACR to detect CKD has not been studied. Moreover, the absence of evidence to determine who would benefit most from CKD screening prohibits investigation of targeted screening programs. Without effective screening programs, our ability to detect CKD and to design and evaluate prevention strategies is limited. This application proposes a paradigm shift in the field of CKD prevention by developing the knowledge necessary to design, evaluate and implement effective CKD screening strategies across diverse populations. Specifically, we propose to pool data from four large, ongoing, NIH-funded cohorts that represent over 27,000 Black and White persons aged 28-84: the Coronary Artery Risk Development in Young Adults (CARDIA), Multi-Ethnic Study of Atherosclerosis (MESA), Reasons for Geographical and Racial Differences in Stroke (REGARDS), and the Health, Aging and Body Composition (Health ABC) Studies. We propose to use these pooled data to implement a triple marker approach to investigate the prevalence of occult CKD among non-diabetics. We will evaluate the numbers needed to screen to detect occult CKD by cystatin C or ACR. Our second goal is to evaluate risk factors associated with occult CKD overall and by age, sex and race/ethnicity. We will then develop a prediction tool for occult CKD and a clinician-friendly, online calculator to estimate an individual's probability of having occult CKD. The data generated from these projects can directly lead to the evaluation of screening strategies that are targeted to individual risk.