Urine Protein Predictors of Nephrolithiasis

肾结石的尿蛋白预测因子

• 批准号: 7422262
• 负责人: JOHN R ASPLIN
• 金额: $ 1.63万
• 依托单位: LITHOLINK CORPORATION
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7422262
• 关键词: biomarker; clinical research; diagnosis design /evaluation; disease /disorder proneness /risk; early diagnosis; enzyme linked immunosorbent assay; human subject; nephrolithiasis; patient oriented research; proteinuria; relapse /recurrence; technology /technique development; urinalysis; urinary tract disorder diagnosis; western blottings

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.

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试验来改善肾结石的医学预防，该试验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，包括常规尿化学测量，是一个穷人的预测病人的风险发展为复发性结石。那些注定要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。我们已经发现三种蛋白质是已知的草酸钙晶体生长的抑制剂，在结石形成者的尿液中显着改变。对钙结石形成者家族成员的初步研究表明，与单独的标准尿化学相比，结合标准尿化学风险因素对这些蛋白质的测量极大地改善了结石形成者与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质的改变可能是结石病活动或复发的标志。我们建议开发改进的Western印迹和ELISA方法来测量这些蛋白质的最高识别形式。我们将通过多次测量一小组结石形成和非结石形成男性和女性的尿液样本，确定测定内和测定间变异性，从而验证这些测定。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尿液并运送到我们实验室的方式近似。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改善了肾结石患者的识别，与传统的尿化学结石风险因素相比，在结石形成家庭内外的人群中，以及在患有不同类型结石的人群中。