Inulin immunoassay for kidney function

描述（由申请人提供）：缺乏一种广泛接受的商业上可用的方法来测量动物模型和临床中的肾小球滤过率（GFR），这对以下方面产生了深远的负面影响：(i)开发治疗肾脏疾病的方法和药物，（ii）准确评估肾移植受体和供体，（iii）校准年轻人和老年人的药物剂量，（iv）在药物开发过程中尽量减少肾毒性，以及(v)在临床环境中准确评估肾毒性。菊粉是测定GFR的金标准。一种灵敏、特异和简便的测定菊粉的方法最有可能被一般研究、临床研究和临床应用所接受。使用免疫测定技术对菊粉进行诊断测试，以测量其从肾脏的清除，为所需的技术和优于所有现有方法的分析工具提供了独特的机会。我们提出了针对菊粉的多克隆抗血清，并建议开发一套试剂，证明用免疫分析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，易于操作，成本有效，高度特异性，并且比目前可用的菊粉测定法灵敏度高得多。我们预期可以制备出一种菊粉的免疫测定方法，其中所有试剂稳定，菊粉的检测下限小于30ng/ml，菊粉抗体的特异性允许区分所有常见糖和多糖（内源性，合成和植物性），抗体滴度大于10,000，检测可在75分钟内完成。所有这些标准都是开发菊粉自动测定法和该测定法商业化所必需的。第二阶段将展示这些试剂在动物模型中测量GFR值的应用。

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.