EPIDEMIOLOGY OF KIDNEY STONE RECURRENCE

肾结石复发的流行病学

• 批准号: 8626068
• 负责人: ANDREW David RULE
• 金额: $ 46.46万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8626068
• 关键词: Accounting; Adult; Affect; Blood Chemical Analysis; Calculi; Candidate Disease Gene; Characteristics; Chemistry; Clinical; Complication; County; Development; Dialysis procedure; Diet; Disease; Electronic Health Record; Epidemiology; Event; Exons; Family; Family history of; Future; General Population; Genes; Genetic; Genomics; Growth; Hyperoxaluria; Image; Inpatients; Instruction; Intervention; Kidney Calculi; Kidney Failure; Laboratories; Lead; Life Style; Manuals; Measurement; Medical; Modeling; Operative Surgical Procedures; Outcome; Outpatients; Pain; Patients; Pattern; Phenotype; Physicians; Population; Prevention strategy; Recruitment Activity; Recurrence; Risk; Sampling; Serology test; Stratification; Testing; Transplantation; Urine; Variant; Work; X-Ray Computed Tomography; base; cohort; experience; genetic analysis; health record; high risk; improved; lifestyle factors; next generation sequencing; novel; prevent; prospective; statistics; tool

PROJECT SUMMARY (See instructions): The objectives of this application are to determine the key environmental and genetic factors that lead to symptomatic recurrence among stone formers, as well as to validate asymptomatic stone formation and growth by CT scan as a surrogate for symptomatic recurrence. The central clinical hypothesis is that kidney stone recurrence can be predicted from clinical, laboratory, and radiographic measurements in the electronic health record (EHR). Our central mechanistic hypothesis is that genomic markers for kidney stones contribute to an increased risk of incident and recurrent stone events. In order to develop effective prevention strategies for kidney stone recurrence, we plan to objectively test our hypotheses with the following aims: Specific Aim #1: To develop a model to better predict symptomatic stone recurrence using clinical and laboratory information from the comprehensive (inpatient and outpatient) health records of 4680 chart validated symptomatic stone formers in the Olmsted County general population (1984 to 2016). Specific Aim #2: To determine if urine chemistries, blood serologies, and life-style factors can improve the prediction of symptomatic recurrence beyond the clinical and laboratory characteristics available in the EHR using 800 incident stone formers in our expanded prospective cohort (2009 to 2017). Specific Aim #3: To determine if models predicting symptomatic recurrence in Aims 1 or 2 also predict radiographic stone formation and growth among 300 incident stone formers in our current prospective cohort. Specific Aim #4: To sample stone formers from the general population to identify causative genes. A) Assemble a cohort of 1500 carefully validated and phenotyped incident kidney stone formers, plus 1500 controls for genetic analysis. Multiplex families will be a focus of this recruitment effort. B) Screen 400 validated incident symptomatic kidney stone formers for significant variants in 66 candidate genes for hypercalcuria, employing exon capture and next generation sequencing.

项目摘要（参见说明）： 该应用的目的是确定导致结石形成者症状复发的关键环境和遗传因素，并通过 CT 扫描验证无症状结石形成和生长作为症状复发的替代指标。核心临床假设是，可以通过电子健康记录 (EHR) 中的临床、实验室和放射线测量来预测肾结石复发。我们的中心机制假设是，肾结石的基因组标记会增加结石事件发生和复发的风险。为了制定有效的肾结石复发预防策略，我们计划客观地检验我们的假设，其目标如下： 具体目标#1：开发一种模型，利用来自综合（住院患者和患者）的临床和实验室信息更好地预测症状性结石复发。门诊）健康记录包含 4680 名经图表验证的奥姆斯特德县一般人群（1984 年至 2016 年）有症状的结石形成者的健康记录。具体目标#2：使用我们扩大的前瞻性队列（2009 年至 2017 年）中的 800 名结石形成者，确定尿液化学、血液血清学和生活方式因素是否可以改善症状复发的预测，超出 EHR 中可用的临床和实验室特征。 ）。具体目标#3：确定预测目标 1 或 2 中症状复发的模型是否也可以预测我们当前前瞻性队列中 300 名结石形成者的放射学结石形成和生长。具体目标#4：从普通人群中抽取结石形成者样本，以确定致病基因。 A) 组建一个由 1500 名经过仔细验证和表型分析的肾结石形成者组成的队列，加上 1500 名对照进行基因分析。多住所家庭将是本次招聘工作的重点。 B) 采用外显子捕获和下一代测序技术，对 400 个经过验证的症状性肾结石形成者进行了 66 个高钙尿症候选基因的显着变异筛查。