Predicting Relapse During Treatment for Nephrolithiasis

描述（由申请人提供）：拟议研究的总体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。我们发现两种已知的草酸钙晶体生长抑制剂蛋白质在结石形成者的尿液中发生了显着改变。我们已经开发了一种蛋白质印迹法来测量尿液中这些蛋白质的各种形式。初步研究表明，与单独的标准尿化学相比，这些蛋白质测量与标准尿化学风险因素的组合大大提高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。我们预测，蛋白质模式可能会改变，以响应减少结石形成的治疗。我们建议使用我们目前的蛋白质印迹法来寻找钙结石形成者的尿液中这些蛋白质在两种常用药物治疗前后的变化，以防止复发性肾结石。我们还将开发一种定量蛋白质印迹法，以提高我们的分析方法的准确性和稳定性。在第二阶段，我们将测试这些测量是否可以用于识别肾结石患者复发的风险，通过寻找这些蛋白质的差异，接受积极的药物治疗的患者之间有或没有结石复发。

DESCRIPTION (provided by applicant): The overall 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 two proteins that are known inhibitors of calcium oxalate crystal growth to be significantly altered in the urine of stone formers. We have developed a western blotting method to measure various forms of these proteins in urine. Preliminary studies have shown that the combination of these protein measurements 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 predict that the protein patterns may change in response to therapies that reduce stone formation. We propose to use our current western blotting method to look for changes in these proteins in the urine of calcium stone formers before and after treatment with two medications commonly used to prevent recurrent nephrolithiasis. We will also develop a quantitative western blotting assay in order to improve the accuracy and stability of our method of analysis. In Phase II we will test whether these measurements can be used to identify kidney stone patients at risk for recurrence by looking for differences in these proteins between patients receiving active drug therapy who have or have not had a relapse of stones.