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试验来改善儿童肾结石的医学预防，该试验可以预测肾结石儿童的结石发展和高钙尿症引起的血尿综合征。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结石。早期诊断和治疗结石或使儿童易患结石的高钙尿症等疾病非常重要，因为这种疾病的终身复发风险和潜在发病率很高。我们发现三种已知的草酸钙晶体生长抑制剂蛋白质在成人结石形成者的尿液中发生了显着改变。对钙结石形成者成年家庭成员的初步研究表明，与单独的标准尿液化学相比，这些蛋白质的测量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。儿童肾结石的患病率低于成人，儿童尿液抑制结晶的能力高于成人。我们建议调查尿结晶特性或特异性抑制蛋白的变化是否与儿童结石病有关，因为它们在成人中。同样，我们计划检查这些因素的变化是否与高钙尿症引起的血尿有关。我们希望确定最能区分非结石形成儿童与结石或高钙尿症伴血尿儿童的检测方法，并询问它们是否可以沿着或代替传统风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.