BIOMARKER FOR EARLY DETECTION OF CHRONIC KIDNEY DISEASE

描述（由申请人提供）：估计有2600万美国人患有早期慢性肾病（CKD）。早期诊断和治疗是扭转这一日益严重的问题的唯一具有成本效益的手段。NIH认识到在CKD的起始和发展阶段早期诊断CKD的挑战，以防止进一步的肾损伤，降低心血管风险，并最大限度地减少CKD的经济影响。目前用于评估CKD的方法和生物标志物在疾病确立后是有效的，但对于早期疾病的检测并不可靠。此外，许多患者最初决定 通过目前的方法，患有肾功能轻度下降的患者实际上可能被错误分类并且可能诊断不足，导致患者患有未诊断的中度至重度肾损伤。我们将生产一种新的CKD ELISA，作为一种诊断测试，基于使用一种新的生物标志物，反映肾脏疾病的病理生理学的早期事件。检测CKD的这种生物标志物将提供实验室结果和临床见解， 是补充肌酐为基础的肾小球滤过率（GFR）的估计，以及测试尿白蛋白。这将导致更可靠和更早地识别CKD。 此外，我们的CKD检测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。在第一阶段，我们评估了该试验的可行性和原理证明，发现两个人群中的原型试验具有高度的灵敏度和特异性。在II期，我们将寻找共病条件和药物对检测性能的影响，将我们的结果与GFR的金标准检测进行比较，并随访患者至少3年，以评估该生物标志物跟踪CKD进展的能力。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。我们请求II期支持，以便我们能够评估原型检测并进一步测试其可行性，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批准并减少诊断不足的CKD的社会影响。

DESCRIPTION (provided by applicant): There are an estimated 26 million Americans with early chronic kidney disease (CKD). Early diagnosis and treatment are the only cost-effective means to reverse this growing problem. 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. Current methods and biomarkers that are used to assess CKD are effective once the disease is well established but are not reliable for the detection of early disease. Further, many patients initially determined to have a mild decline in kidney function by the current methods may actually be misclassified and possibly under-diagnosed, resulting in a patient having undiagnosed moderate to severe kidney damage. We will produce a new ELISA for CKD to be employed as a diagnostic test based upon the use of a novel biomarker that reflects early events in the pathophysiology of kidney disease. Detection of this biomarker for CKD will give laboratory results and clinical insight that are complementary to creatinine-based glomerular filtration rate (GFR) estimates as well as tests for urine albumin. This should result is a more reliable and earlier identification of CKD. n addition, our CKD-Assay would give physicians the ability to evaluate patients that have been recently diagnosed with hypertension or diabetes. In Phase I, we evaluated the feasibility and proof-of principal of this test and found that the prototype assay in both populations was highly sensitive and specific. In Phase II, we will look for the influence of comorbid conditions and medications on assay performance, compare our results to the gold standard assay of GFR, and follow up patients over at least 3 years to evaluate the ability of this biomarker to follow progression of CKD. Lastly, we will evaluate whether patient characteristics such as age, gender, BMI, ethnicity, and other factors impact on assay performance. We request Phase II support so that we can evaluate the prototype assay and further test its feasibility to help identiy at-risk patients for early kidney disease and monitor therapy with the ultimate goal of obtaining FDA approval and reducing the societal impact of under-diagnosed CKD.