Inulin immunoassay for kidney function

描述(申请人提供)：在动物模型和临床中，缺乏一种被广泛接受的可用于测量肾小球滤过率(GFR)的商业方法，这对(I)开发治疗肾脏疾病的方法和药物，(Ii)准确评估肾移植受者和捐赠者，(Iii)校准年轻人和老年人的药物剂量，(Iv)将药物开发过程中的肾毒性降至最低，以及(V)在临床环境中准确评估肾毒性，产生了深远的负面影响。菊粉是测量肾小球滤过率的黄金标准。一种灵敏、特异和简便的菊粉测定方法最有可能被一般研究、临床研究和临床应用所接受。使用免疫分析技术对菊粉进行诊断测试，以测量其从肾脏中的清除量，为所需的技术和分析工具提供了一个独特的机会，优于所有当前的方法。我们提出了菊粉的多克隆抗血清，并建议开发一套试剂，以证明免疫测定法测定菊粉的可行性。菊粉免疫测定法避免了其他菊粉测定法的缺点，而且操作简单、成本效益高、特异性高，而且比目前可用的菊粉测定法更灵敏。我们预计可以生产一种菊粉免疫分析方法，其中所有试剂都是稳定的，菊粉的检测下限小于30 ng/ml，菊粉抗体的特异性允许区分所有常见的糖和多糖(包括内源、合成和植物来源的)，抗体效价大于10,000，并且检测可以在75分钟内完成。所有这些标准对于菊粉自动化检测的发展和该检测的商业化都是必要的。第二阶段将演示试剂在动物模型中测量GFR值的应用。 与公共卫生相关：该项目将进一步开发一种诊断测试来测量肾功能。这项测试将利用众所周知和广泛可用的分析技术，并将使用“黄金标准”来测量肾功能。因此，这一测试将能够迅速进入市场。

DESCRIPTION (provided by applicant): The absence of a widely accepted commercially available method to measure glomerular filtration rate (GFR) in animal models and in the clinic has had profoundly negative effects on (i) developing methods and drugs for treating kidney disease, (ii) accurately assessing kidney transplant recipients and donors, (iii) calibrating drug dosing in the young and elderly, (iv) minimizing nephrotoxicity in the drug development process, and (v) accurately assessing nephrotoxicity in the clinical setting. Inulin is the gold standard for measuring GFR. A sensitive, specific and easy assay to measure inulin is most likely to be accepted for general research, clinical research, and clinical applications. A diagnostic test for inulin using immunoassay techniques to measure its clearance from the kidney offers a unique opportunity for a needed technology and an analytical tool superior to all current methods. We have raised polyclonal antisera to inulin and propose to develop a set of reagents that demonstrate the feasibility of measuring inulin using immunoassay. An inulin immunoassay avoids the shortcomings of other inulin assays and is easy to perform, cost effective, highly specific, and far more sensitive than currently available inulin assays. We anticipate that an immunoassay for inulin can be produced wherein all the reagents are stable, the lower limit of detection of inulin is less than 30ng/ml, the specificity of the antibody for inulin allows discrimination between all common sugars and polysaccharides (both endogenous, synthetic, and botanical), the antibody titer is greater than 10,000, and the assay can be completed within 75 minutes. All of these criteria are necessary for the development of an automated assay for inulin and the commercialization of this assay. Phase II will demonstrate the application of the reagents to measuring GFR values in animal models. PUBLIC HEALTH RELEVANCE: The project will further develop a diagnostic test to measure kidney function. The test will utilize well-known and widely available analytical technology and will utilize the "gold standard" for the measure of kidney function. Therefore, this test will be able to quickly enter the market-place.