Biomarker for Early Detection of Chronic Kidney Disease

描述（由申请人提供）：本提案是根据项目公告PA-09-080“NIH， CDC和FDA小企业创新研究资助申请的综合征集（母SBIR [R43/R44]）”提交的，旨在直接提交给NIDDK，并可能向NHLBI分配双重任务。据估计，有1400万美国人患有早期慢性肾病（CKD）。早期诊断和治疗慢性肾病是扭转这一日益严重的问题的唯一经济有效的方法。目前用于评估CKD的方法和生物标志物在疾病确定后是有效的，但迄今为止，没有一种方法和生物标志物对早期肾脏疾病的检测是可靠的。目前医生使用的现有测试基本上都是肾脏滤过功能的标记。通过PA-09-204（疾病生物标志物的开发和验证）和PA-09-181（糖尿病、肾脏、泌尿、血液和消化系统疾病的无创诊断和进展方法）等项目公告，NIH认识到在CKD的启动和发展阶段早期诊断CKD的挑战，以防止进一步的肾脏损害，降低心血管风险，并最大限度地减少CKD的经济影响。我们将基于一种新的生物标志物的使用，在一定程度上反映肾脏疾病的病理生理学，生产一种新的CKD ELISA。检测这种CKD的生物标志物将提供实验室结果和临床见解，这是对基于肌酐的GFR估计（eGFR）以及尿白蛋白测试的补充。该测试的发展将导致更可靠的早期CKD患者的识别和检测。此外，我们的CKD ELISA将使医生能够评估最近被诊断患有高血压或糖尿病的患者，这是CKD的两个主要原因。接下来，该I期提案将在这两个人群中评估原型试验。我们将寻找合并症和药物对分析性能的影响。最后，我们将评估患者特征，如年龄、性别、BMI、种族和其他因素是否会影响检测性能。从该试验中获得的信息也将有助于更好地了解CKD的生物学机制。Sequela请求I期支持，以便我们可以评估原型分析并测试其可行性，以帮助识别早期肾脏疾病的高危患者并监测治疗，最终目标是获得FDA批准。

DESCRIPTION (provided by applicant): This proposal is submitted in response to the program announcement PA-09-080, "Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44])" and intended to be directed to the NIDDK, with a potential dual assignment to the NHLBI. There are an estimated 14 million Americans with early chronic kidney disease (CKD). Early diagnosis and treatment of CKD are the only cost-effective means to reverse this growing problem. Current methods and biomarkers that are used to assess CKD are effective once the disease is well established, but none, thus far, are reliable for the detection of early renal disease. Existing tests used by physicians today are all essentially markers of kidney filtration function. NIH recognizes the challenge to diagnose CKD early during its initiation and development phases in order to prevent further renal damage, reduce cardiovascular risk, and minimize the economic impact of CKD through program announcements such as PA-09-204 (Development and Validation of Disease Biomarkers) and PA-09-181 (Non-Invasive Methods for Diagnosis and Progression of Diabetes, Kidney, Urological, Hematological and Digestive Diseases). We will produce a new ELISA for CKD based upon the use of a novel biomarker that reflects, in part, the pathophysiology of kidney disease. Detection of this biomarker for CKD will give laboratory results and clinical insight that is complementary to creatinine-based GFR estimates (eGFR) as well as tests for urine albumin. Development of this test should result in a more reliable identification and detection of early CKD patients. In addition, our CKD ELISA would give physicians the ability to evaluate patients that have been recently diagnosed with hypertension or diabetes, the two leading causes of CKD. In turn, this Phase I proposal will evaluate the prototype assay in both populations. We will look for the influence of comorbid conditions and medications on assay performance. Lastly, we will evaluate whether patient characteristics such as age, gender, BMI, ethnicity, and other factors impact on assay performance. The information gained from this test will also lead to a better basic understanding of the biological mechanisms underlying CKD. Sequela requests Phase I support so that we can evaluate a prototype assay and test its feasibility to help identify at-risk patients for early kidney disease and monitor therapy with the ultimate goal of obtaining FDA approval. PUBLIC HEALTH RELEVANCE: Chronic Kidney Disease affects nearly 26 million people in the United States, which places them at higher risk of renal failure and hemodialysis. We will develop an ELISA to aid in the diagnosis of early kidney disease to aid physicians in earlier treatment and better assessment of chronic kidney disease.