Urine Crystal Inhibition in Pediatric Nephrolithiasis

描述(申请人提供)：拟议研究的科学和商业目标是通过开发新的临床测试方法来改善儿童肾结石的医学预防，该方法可以预测肾结石儿童的结石发展和高钙尿引起的血尿综合征。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患结石的风险。早期诊断和治疗结石，或使儿童易患结石的高钙尿症等情况非常重要，因为这种疾病具有终身复发的高风险和潜在的发病率。我们发现三种已知的抑制草酸钙晶体生长的蛋白质在成年结石患者的尿液中发生了显着变化。对钙结石形成者成年家庭成员的初步研究表明，与标准的尿液化学分析相比，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别。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。儿童的肾结石患病率比成人低，儿童的尿液比成人的尿液具有更强的抑制结晶的能力。我们建议调查尿液结晶特性或特定抑制蛋白的变化是否与儿童结石疾病有关，就像在成人中一样。同样，我们计划检查这些因素中的任何一个的变化是否与高钙尿所致的血尿有关。我们希望找出最能区分非结石形成儿童和结石或高钙尿伴血尿的儿童的方法(S)，并询问它们是否可以与传统的危险因素一起使用或替代传统的危险因素来改善这些疾病状态的管理。

DESCRIPTION (provided by applicant): The scientific and commercial objective of the proposed research is to improve the medical prevention of kidney stones in children by developing new clinical assays that can predict the development of stones in children with nephrolithiasis and the syndrome of hematuria due to hypercalciuria. Currently available technology, consisting of routine urine chemistry measurements, is a poor predictor of a patient's risk for developing stones. Early diagnosis and treatment of stones, or conditions such as hypercalciuria that predispose children to stones, is important because of the high life-long risk of recurrence and potential morbidity of the disease. We have found three proteins that are known inhibitors of calcium oxalate crystal growth to be significantly altered in the urine of adult stone formers. Preliminary studies of adult family members of calcium stone formers have shown that measurements of these proteins 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 markers of stone disease activity or vulnerability to recurrence. Children have a lower prevalence of nephrolithiasis than adults, and urine from children has a greater ability to inhibit crystallization than that of adults. We propose to investigate whether variations in urine crystallization properties or in specific inhibitor proteins are associated with stone disease in children as they are in adults. Likewise, we plan to examine whether variations in any of these factors are linked with hematuria due to hypercalciuria. We wish to identify the assay(s) that best discriminate non stone forming children from those with stones or hypercalciuria with hematuria, and to ask whether they can be used along with or instead of conventional risk factors to improve the management of these disease states.