Improving stone disease treatment by accurate phenotyping and risk stratification

描述(由申请者提供)：梅奥临床泌尿外科奥布莱恩研究中心的总体目标是开发新的诊断策略，以便准确地对患者进行表型分析，从而应用改进的个性化管理策略。我们将通过4个相互关联的多学科项目来实现这些目标。梅奥诊所奥布莱恩泌尿外科研究中心的重要和及时的目标包括： 1)利用临床双能CT技术开发和验证一种全面的低剂量结石定性检查，以预测结石的脆性，并开发新的CT方法，能够发现最早的可能的先兆病变。 2)确定导致NL前驱病变的因素，包括Randall‘s斑块和管状栓子。 3)明确增加肾结石及其复发风险的具体因素，并开发临床预测工具，帮助临床医生识别高危患者。 4)在一个新的高通量果蝇模型中确定影响草酸运输和结晶的环境和遗传因素。 这一建议是对奥布莱恩泌尿外科研究中心RFA的高度响应，该中心将经验丰富的临床医生和基础科学家组成的真正多学科小组聚集在一起，进行转化性研究。每个项目都是多学科的，临床研究、转化研究和基础研究都得到了很好的体现。此外，所有项目都有明确的临床相关性，并将影响我们对肾结石的理解和我们护理患者的能力。梅奥诊所拥有独特的资源集合，如罗切斯特流行病学项目；拥有遗传学、蛋白质组学和运输生理学专业知识的资助实验室；大量患者；以及可应用于这种常见但研究不足的疾病的CT成像创新中心。通过这个奥布莱恩中心，现有的泌尿学、肾脏学、放射学、流行病学、遗传学和生理学方面的临床和基础科学专业知识将协同工作，促进快速发展。

DESCRIPTION (provided by applicant): The overall goals of the Mayo Clinic Urology O'Brien Research Center are to develop new diagnostic strategies in order to accurately phenotype patients and thus apply improved individualized management strategies. We will pursue these goals via 4 interlinked multidisciplinary projects. Important and timely aims of the Mayo Clinic O'Brien Urology Research Center include: 1) Develop and validate a comprehensive low-dose stone-characterization exam using clinical dual-energy CT techniques in order to predict stone fragility, and to develop new CT methods capable of detecting the earliest possible precursor lesions. 2) Determine factors that produce NL precursor lesions including Randall's plaques and tubular plugs. 3) Define specific factors that increase the risk of kidney stones and their recurrence, and develop clinical prediction tools to help clinicians identify high-risk patients. 4) Define environmental and genetic factors that influence oxalate transport and crystallization in a novel high throughput Drosophila model. This proposal is highly responsive to the O'Brien Urology Research Center RFA bringing together truly multidisciplinary group of experienced clinicians and basic scientists to conduct translational research. Each project is multidisciplinary, and clinical, translational and basic research is each well represented. Further, all projects have clear clinical relevance and will impact our understanding of nephrolithiasis and our ability to care for patients. The Mayo Clinic has a unique collection of resources such as the Rochester Epidemiology Project; funded laboratories with expertise in genetics, proteomics and transport physiology; large patient volumes; and the CT Imaging Innovation Center which can be applied to this common yet understudied disorder. Through this O'Brien Center, existing clinical and basic science expertise in urology, nephrology, radiology, epidemiology, genetics and physiology will work in synergy to foster rapid progress.