Primary Hyperoxaluria

原发性高草酸尿症

• 批准号: 7934947
• 负责人: Dawn Schmautz Milliner
• 金额: $ 50.5万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-08 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7934947
• 关键词: Address; Area; Betaine; Calculi; Childhood; Clinical; Clinical Data; Clinical Research; Clinical Trials; Collaborations; Cystinuria; Databases; Disease; Educational Materials; End stage renal failure; European; Foundations; Future; Genes; Genetic; Goals; Health Personnel; Hydroxyproline; Hyperoxaluria; Information Resources; Inherited; Injury; Instruction; International; Kidney; Kidney Failure; Medical; Metabolic; Molecular; Nephrocalcinosis; Nephrolithiasis; Online Systems; Outcome; Oxalates; Oxalobacter; Patient Care; Patients; Physicians; Pilot Projects; Primary Hyperoxaluria; Rare Diseases; Registries; Renal function; Research; Research Personnel; Scientist; Screening procedure; Site; Structure; Testing; Tissue Banking; Tissue Banks; cohort; early onset; effective therapy; experience; follow-up; improved; innovation; investigator training; oxalosis; tissue resource; treatment strategy

PROJECT SUMMARY (See instructions): Primary hyperoxaluria (PH) is the most severe of the stone diseases, causing recurring stones from childhood on and end stage renal failure. Progress toward effective treatments has been slow. Our experience with the International Primary Hyperoxaluria Registry (IPHR) has resulted in better understanding of disease expression, early recognition of factors associated with loss of renal function, has suggested treatment strategies likely to be successful, and has facilitated sufficient numbers of patients to test new treatments in clinical trials of betaine and Oxalobacter, to date. The goals of the current project are to: (1) Expand our current PH registry to determine the factors associated with nephrocalcinosis, stone formation, and renal injury (2) Generate testable hypotheses regarding mechanisms of renal injury in these diseases through registry findings, tissue resources, and pilot projects. (3) Explore new avenues of treatment. (4) Develop cohorts of well-characterized patients for future clinical studies, (5) Explore new areas of partnership with the Oxalosis and Hyperoxaluria Foundation (OHF) (6) Provide ready access to high quality resources and information for physicians and scientists and (7) Attract and train investigators to rare diseases research. We will accomplish these goals through a consortium of clinician and basic scientists expert in PH, a network of study sites, and close collaboration with the OHF to more effectively reach and educate health care providers and patients. The 4 Specific Aims are to: S.A. 1a. Expand the PH registry containing clinical data for longitudinal follow-up of patients, identifying wellcharacterized cohorts of patients available for future treatment studies. 1 b. Expand the PH tissue bank S.A. 2a. Identify genetic modifiers of disease expression, specifically early onset of ESRD 2b. Perform molecular screening of TGF p as a candidate modifier gene. S.A. 3. Evaluate hydroxyproline as a potential metabolic precursor of oxalate in PH types 1 and 2. S.A. 4a. Create web-based educational materials at the highest scientific and medical level, to allow creation of patient material by the Oxalosis and Hyperoxaluria Foundation for international dissemination. 4b. Provide high quality information and resources regarding PH for physicians, clinical and basic scientists. We will also apply our experience with the IPHR to create a similar structure and activities for other hereditary causes of nephrolithiasis and renal failure: cystinuria, APRT deficiency, and Dent disease. Synergies will allow rapid transfer of experience and advancement of patient care.

项目总结(见说明)： 原发性高草酸尿症(PH)是最严重的结石疾病，可导致结石复发。 儿童期和终末期肾功能衰竭。在有效治疗方面进展缓慢。我们的 国际高草酸尿症登记(IPHR)的经验使我们更好地了解 疾病表现，早期识别与肾功能丧失相关的因素，已经表明 治疗策略可能成功，并已促进了足够数量的患者测试新的 甜菜碱和草酸杆菌的临床试验治疗，到目前为止。当前项目的目标是：(1) 扩展我们目前的PH登记，以确定与肾钙沉着、结石形成、 和肾损伤(2)产生了关于这些疾病的肾损伤机制的可检验的假说 通过登记结果、组织资源和试点项目。(三)探索治疗新途径。(4) 为未来的临床研究开发具有良好特征的患者队列，(5)探索新的领域 与草酸中毒和高草酸尿症基金会(OHF)(6)的合作伙伴关系提供随时获得高质量的机会 为医生和科学家提供的资源和信息以及(7)吸引和培训研究人员到REARE 疾病研究。我们将通过一个由临床医生和基础科学家组成的联盟实现这些目标 PH专家，一个研究地点网络，并与OHF密切合作，以更有效地接触和 教育卫生保健提供者和患者。四个具体目标是： S.A.1A。扩展PH注册表，包含用于对患者进行纵向随访的临床数据，确定具有良好特征的 可用于未来治疗研究的患者队列。1b.扩充PH组织库 S.A.2A号。确定疾病表达的遗传修饰因素，特别是ESRD的早期发病 2B。对作为候选修饰基因的转化生长因子β进行分子筛选。 评估羟脯氨酸在PH1和PH2中作为草酸的潜在代谢前体的作用。 S.A.4A.在最高科学和医学水平上创建基于网络的教育材料，以允许创建 由草酸缺乏症和高草酸尿症基金会为国际传播的患者材料。 4B.为医生、临床和基础科学家提供有关PH的高质量信息和资源。 我们还将应用我们在IPHR方面的经验，为其他 肾结石和肾功能衰竭的遗传性原因：胱氨酸尿症、APRT缺乏症和齿状神经病。 协同效应将使经验的快速转移和病人护理的进步。