Urine Crystal Inhibition in Pediatric Nephrolithiasis

描述（由申请人提供）：拟议研究的科学和商业目的是通过开发新的临床检测方法来预测肾结石患儿的结石发展和高钙尿血尿综合征，从而改善儿童肾结石的医学预防。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患结石的风险。早期诊断和治疗结石，或者像高钙尿症这样易使儿童患结石的疾病，是很重要的，因为这种疾病的终生复发和潜在发病率的风险很高。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有显著改变。对钙质结石患者的成年家庭成员的初步研究表明，与单独的标准尿液化学物质相比，测量这些蛋白质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作为结石疾病活动或复发易感性的标志。儿童肾结石的患病率低于成人，儿童尿液抑制结晶的能力也高于成人。我们建议研究尿结晶特性或特定抑制剂蛋白的变化是否与儿童结石疾病相关，就像在成人中一样。同样，我们计划检查这些因素的变化是否与高钙尿引起的血尿有关。我们希望确定能够最好地区分非结石形成儿童与结石或高钙尿伴血尿儿童的检测方法，并询问它们是否可以与常规危险因素一起使用或代替传统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.