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测试方法来改善肾结石的医学预防，该方法可以预测这种慢性且昂贵的疾病患者的肾结石复发。目前可用的技术，包括常规的尿液化学测量，不能很好地预测患者复发结石的风险。那些注定会复发的患者将受益于可以提前识别他们的测试，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形成者的尿液中发生了显着变化。对钙结石形成者家族成员的初步研究表明，与单独进行标准尿液化学检查相比，对这些蛋白质的测量与标准尿液化学危险因素相结合，极大地改善了对结石形成者和非结石形成者的区分。我们的假设是，肾结石患者尿液中这些蛋白的变化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法来测量这些蛋白质的最高分辨形式。我们将通过对一小部分结石形成和非结石形成的男性和女性的尿样进行多次测量来确定试剂盒内和试剂盒间的可变性，从而验证这些检测方法。我们还将使用这些样本来评估蛋白质在不同储存条件下的稳定性，这些储存条件与目前收集和运送到我们实验室的尿液的方式大致相同。在第二阶段，我们将使用这些分析和条件来前瞻性地测试，与结石形成家庭内外以及不同类型结石患者的传统尿液化学结石风险因素相比，这些蛋白质测量是否可以提高肾结石患者的识别能力。

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.