Urine Protein Predictors of Nephrolithiasis

描述（由申请人提供）：拟议研究的科学和商业目标是通过开发一种新的临床检测方法来改善肾结石的医学预防，该方法可以预测患有这种慢性和昂贵疾病的患者的肾结石复发。目前可用的技术，包括常规尿液化学测量，不能很好地预测患者复发性结石的风险。那些注定会复发的病人将受益于能够提前识别他们的检测，以便及早实施治疗或预防。我们发现三种已知的抑制草酸钙晶体生长的蛋白质在结石患者的尿液中显著改变。对钙质结石患者家庭成员的初步研究表明，与单独使用标准尿液化学物质相比，测量这些蛋白质结合标准尿液化学危险因素大大提高了对结石患者和非结石患者的区分。我们的假设是，肾结石患者尿液中这些蛋白的改变可能是结石疾病活动或复发易感性的标志。我们建议开发改进的western blotting和ELISA方法来测量这些蛋白的最高鉴别形式。我们将通过对一小组结石形成和非结石形成的男性和女性的尿液样本进行多次测量，来确定测定内和测定间的变异性，从而验证这些分析。我们还将使用这些样品来评估蛋白质在不同储存条件下的稳定性，这些条件近似于目前收集尿液并运送到我们实验室的方式。在第二阶段，我们将使用这些检测和条件来前瞻性地测试这些蛋白质测量是否能改善肾结石患者的识别，与传统的尿化学结石危险因素相比，在结石形成家族内外的人群中，以及在不同类型的结石患者中。

DESCRIPTION (provided by applicant): The scientific and commercial objective of the proposed research is to improve the medical prevention of nephrolithiasis by developing a new clinical assay that can predict the recurrence of kidney stones in patients with this chronic and costly disease. Currently available technology, consisting of routine urine chemistry measurements, is a poor predictor of a patient's risk for developing recurrent stones. Those patients destined to recur would benefit from tests that could identify them in advance so that therapy or prevention could be implemented early. We have found three proteins that are known inhibitors of calcium oxalate crystal growth to be significantly altered in the urine of stone formers. Preliminary studies of family members of calcium stone formers have shown that measurements of these proteins combined with standard urine chemistry risk factors vastly improved the discrimination of stone formers from non stone formers compared to standard urine chemistries alone. Our hypothesis is that alterations in these proteins in the urine of kidney stone patients may serve as a marker of stone disease activity or vulnerability to recurrence. We propose to develop improved western blotting and ELISA methods to measure the most highly discriminating forms of these proteins. We will validate these assays by determining intraassay and interassay variability through multiple measurements of urine samples from a small set of stone forming and non stone forming men and women. We will also use these samples to evaluate the stability of the proteins under different storage conditions that approximate the way urine is currently collected and shipped to our laboratory. In Phase II, we will use these assays and conditions to prospectively test whether these protein measurements improve the identification of kidney stone patients compared to conventional urine chemistry stone risk factors in people within and outside of stone forming families, and in people with different types of stones.