Primary Hyperoxaluria

原发性高草酸尿症

• 批准号: 8381379
• 负责人: Dawn Schmautz Milliner
• 金额: $ 50.29万
• 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/8381379
• 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; 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; Resources; 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.

项目摘要（请参阅说明）： 原发性高黄油（pH）是最严重的石材疾病，导致重复发生的石头 童年时期和终结阶段的肾衰竭。朝着有效治疗方面的进展很慢。我们的 具有国际初级高黄油注册表（IPHR）的经验，使得更好地理解 疾病表达，早期识别与肾功能丧失相关的因素，已经表明 治疗策略可能会成功，并促进了足够数量的患者来测试新的 迄今为止，在贝甲基和草酸菌的临床试验中的治疗方法。当前项目的目标是：（1） 扩展我们当前的pH注册中心，以确定与肾球身病，石材形成， 肾脏损伤（2）产生有关这些疾病肾脏损伤机制的可检验的假设 通过注册表发现，组织资源和试点项目。 （3）探索新的治疗途径。 （4） 开发良好特征的患者的同类群体进行未来的临床研究，（5）探索的新领域 与Oxalisos和Hyperoxaluria Foundation（OHF）（6）的合作伙伴关系可用 医师和科学家的资源和信息，（7）吸引和培训调查人员罕见 疾病研究。我们将通过临床医生和基础科学家的联盟来实现这些目标 PH（研究网站网络）的专家，并与OHF密切合作，以更有效地达到和 教育医疗保健提供者和患者。 4个具体目标是： S.A. 1a。扩展包含患者纵向随访的临床数据的pH注册中心，确定了良好的表现 可用于将来治疗研究的患者队列。 1 b。扩展pH组织库 S.A. 2a。鉴定疾病表达的遗传修饰符，特别是ESRD的早期发作 2b。对TGF P进行分子筛选作为候选修饰符基因。 S.A. 3。评估羟基丙烯酸盐作为Oxalate的潜在代谢前体，在pH 1和2型中。 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，以创建 大氧症和高黄油尿症基金会的国际传播基础的患者材料。 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。 我们还将运用IPHR的经验，为其他人创建类似的结构和活动 肾结石病和肾衰竭的遗传原因：囊肿，APRT缺乏和凹陷疾病。 协同作用将允许快速转移经验和患者护理的进步。