Primary Hyperoxaluria

项目总结（见说明）： 原发性高尿酸血症（PH）是最严重的结石疾病，可导致结石复发， 儿童期和终末期肾衰竭。有效治疗的进展一直很缓慢。我们 国际原发性高尿酸血症登记处（IPHR）的经验使我们更好地了解 疾病的表达，早期识别与肾功能丧失相关的因素， 治疗策略可能是成功的，并促进了足够数量的患者测试新的 甜菜碱和草酸钙的临床试验治疗，迄今为止。本项目的目标是：（1） 扩大我们目前的PH登记，以确定与肾钙质沉着、结石形成、 （2）提出关于这些疾病中肾损伤机制的可检验假设 通过登记研究结果、组织资源和试点项目。(3)探索新的治疗途径。（四） 为未来的临床研究开发特征良好的患者队列，（5）探索新的研究领域。 与草酸盐症和高尿酸症基金会（OHF）建立伙伴关系（6） 为医生和科学家提供资源和信息;（7）吸引和培训研究人员， 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来实现这些目标 PH专家，研究中心网络，并与OHF密切合作，以更有效地达到和 教育卫生保健提供者和患者。四个具体目标是： S.A. 1a.扩展包含患者纵向随访临床数据的PH登记研究，识别特征良好的 可用于未来治疗研究的患者队列。1 B。扩大PH组织库 S.A. 2a.识别疾病表达的遗传修饰因子，特别是ESRD的早期发作 2b.进行TGF β作为候选修饰基因的分子筛选。 S.A. 3.评估羟脯氨酸作为PH 1和PH 2型中草酸盐的潜在代谢前体。 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， 由草酸盐症和高尿症基金会收集患者材料，供国际传播。 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。 我们还将运用我们在IPHR的经验，为其他组织创建类似的结构和活动。 肾结石和肾衰竭的遗传原因：胱氨酸尿症、APRT缺乏症和登特病。 协同作用将使经验的快速转移和病人护理的进步。

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.