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脏疾病(CKD)。早期诊断和治疗是扭转这一日益严重的问题的唯一经济有效的手段。美国国立卫生研究院认识到在慢性肾脏病的发病和发展阶段进行早期诊断的挑战，以防止进一步的肾脏损害，降低心血管风险，并将慢性肾脏病的经济影响降至最低。目前用于评估CKD的方法和生物标记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 根据目前的方法，肾功能有轻微下降的患者实际上可能被错误地分类，并可能被低估，导致患者有未被诊断的中度到严重的肾脏损害。我们将生产一种新的用于慢性肾脏病的酶联免疫吸附试验，作为一种诊断试验，基于一种新的反映肾脏疾病病理生理早期事件的生物标志物的使用。检测CKD的这种生物标记物将提供实验室结果和临床洞察力 是对基于肌酐的肾小球滤过率(GFR)估计以及尿白蛋白检测的补充。这应该会使CKD得到更可靠和更早的诊断。此外，我们的CKD-Assay将使医生能够评估最近被诊断为高血压或糖尿病的患者。在第一阶段，我们评估了这项测试的可行性和原则性证明，发现两个群体的原型测试都具有高度的敏感性和特异性。在第二阶段，我们将寻找共存条件和药物对检测性能的影响，将我们的结果与GFR的黄金标准检测进行比较，并对患者进行至少3年的随访，以评估该生物标记物跟踪CKD进展的能力。最后，我们将评估患者的特征，如年龄、性别、体重指数、种族和其他因素是否影响分析性能。我们请求第二阶段的支持，以便我们可以评估原型试验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的批准，并减少诊断不足的CKD的社会影响。 公共卫生相关性：慢性肾脏疾病影响着美国近2600万人，这使他们面临更高的心血管疾病和血液透析风险。我们将开发一种方法来识别目前方法诊断不足的晚期肾脏疾病患者，并帮助医生进行早期治疗和更好地评估慢性肾脏疾病。

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. PUBLIC HEALTH RELEVANCE: Chronic Kidney Disease affects nearly 26 million people in the United States, which places them at higher risk of cardiovascular disease and hemodialysis. We will develop an assay for the identification of people with advanced kidney disease that are under-diagnosed by current methods and to aid physicians in earlier treatment and better assessment of chronic kidney disease.