Plaques and Plugs: Pathogenesis and Relationship to Nephrolithiasis

斑块和栓塞：发病机制及其与肾结石的关系

• 批准号: 10246877
• 负责人: JAMES E LINGEMAN
• 金额: $ 12.87万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10246877
• 关键词: Address; Adult; Apatites; Appearance; Biopsy; Calcium; Calcium Oxalate; Childhood; Chronic; Chronic Kidney Failure; Cimetidine; Classification; Clinical; Creatinine clearance measurement; Crystallization; Disease; Disease susceptibility; Duct (organ) structure; Endoscopy; Event; Excision; Flank Pain; Functional disorder; Gender; Histologic; Histology; Histopathology; Inflammation; Inflammatory; Injury; Injury to Kidney; Intervention; Intrinsic factor; Kidney; Kidney Calculi; Kidney Papilla; Knowledge; Language; Link; Measurable; Measures; Microalbuminuria; Microscopic; Nephrolithiasis; Obstruction; Operative Surgical Procedures; Outcome; Pain; Papillary; Pathogenesis; Pathology; Pathway interactions; Patient Care; Patients; Pattern Formation; Pediatric cohort; Phenotype; Physiology; Plug-in; Process; Provider; Recurrence; Renal function; Reproducibility; Research; Resources; Risk; Risk Factors; Salvelinus; Secondary to; Side; Standardization; Symptoms; System; Testing; Time; Tissues; Tubular formation; Urinary Calculi; Urine; Urologist; Visual; base; calcium phosphate; clinical practice; improved; inflammatory marker; insight; metabolic abnormality assessment; microCT; novel; pain score; prospective; therapy development; tongue papilla; tool; urinary

Summary Project 2 will test the hypothesis that injury to the renal papilla as documented by our papillary injury grading system (PGS) will reflect and predict stone disease, specifically we will determine the influence of intrinsic patient factors such as renal physiology and stone passage events, as well as on the influence of extrinsic patient factors, particularly surgical treatments. To investigate the time course of papillary disease, we will quantify the extent of papillary changes in a co-hort of pediatric calcium stone formers. We will test the hypothesis that our PGS will predict calcium stone type, as well as the relative percentage of calcium phosphate present in stones. In a related hypothesis, we will test whether application of the PGS is able to predict calcium stone type as classified by formation pattern (tubular plugging vs plaque overgrowth). We hypothesize that papilla with high injury scores will correlate with renal injury as quantified by cimetidine blocked creatinine clearance and microalbuminuria. We have documented that tubular plugging is histologically associated with significant inflammatory changes in the papilla. We will test the hypothesis that these changes will be reflected by elevated levels of inflammatory markers in urine, as well as tissue. We have previously documented that percantage of Randall's plaque papillary coverage correlates directly with stone activity. We will determine whether papillary injury is also associated with stone activity. Finally, we will test the hypothesis that inflammation secondary to ductal plugging is associated with chronic flank pain in the setting of non-obstructing renal stones and, further, whether the treatment of such stones is associated with improvement in patient symptoms. RELEVANCE

概括 项目 2 将检验我们的乳头损伤所记录的肾乳头损伤的假设 分级系统（PGS）将反映和预测结石病，具体来说我们将确定以下因素的影响： 患者的内在因素，例如肾脏生理学和结石排出事件，以及对 患者的外在因素，尤其是手术治疗。研究乳头状的时间进程 疾病，我们将量化一组儿童钙结石形成者的乳头状变化程度。我们 将测试我们的 PGS 将预测钙结石类型以及相对百分比的假设 磷酸钙存在于结石中。在相关假设中，我们将测试 PGS 的应用是否 能够预测钙结石类型，按形成模式分类（管状堵塞与斑块 过度生长）。我们假设具有高损伤评分的乳头与肾损伤相关： 通过西咪替丁阻断肌酐清除率和微量白蛋白尿进行定量。我们已经记录了 管状堵塞在组织学上与乳头的显着炎症变化相关。我们将 检验以下假设：这些变化将通过体内炎症标志物水平升高得到反映 尿液，以及组织。我们之前已经记录了兰德尔斑块乳头状的百分比 覆盖率与结石活性直接相关。我们将确定是否也有乳头损伤 与石材活动有关。最后，我们将检验继发于导管的炎症的假设 在非梗阻性肾结石的情况下，堵塞与慢性胁腹痛有关，而且， 此类结石的治疗是否与患者症状的改善有关。 关联