Prevention of Renal Damage in Primary Hyperoxaluria

原发性高草酸尿症肾损伤的预防

• 批准号: 7017453
• 负责人: Dawn Schmautz Milliner
• 金额: $ 45.47万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7017453
• 关键词: alpha globulin; biomarker; clinical research; disease /disorder proneness /risk; genetic registry /resource /referral center; glutamyltransferase; glycolates; human data; human subject; kidney disorder; kidney function; longitudinal human study; nephrocalcinosis; oxalates; pathologic process; patient /disease registry; pharmacogenetics; primary hyperoxalurias; retinoid binding proteins; technology /technique development; transforming growth factors

DESCRIPTION (provided by applicant): Primary hyperoxaluria (PH) is a rare autosomal recessive disorder (estimated incidence 1:120,000 births). While most patients experience nephrocalcinosis and/or repeated episodes of urolithiasis in childhood, some develop renal failure as early as infancy while others first present as adults with urolithiasis only. The reasons for such disparity are largely unknown. However, the majority, if not all, PH patients eventually lose renal function and require renal transplantation with liver transplantation also needed in most. There is an urgent need for identification of factors responsible for severe disease expression, and for effective treatments. Progress in understanding the pathophysiology of hyperoxaluria and associated renal injury and in development of effective treatments, has been slowed by the rarity of this condition. The overall objective of this grant is to pool patient experience in order to identify factors associated with disease progression in PH, modify them using specific treatment strategies in patients at risk, and demonstrate reduction in renal injury. We have assembled a unique group of physicians and scientists with longstanding interest in PH. Recently we developed a secure, web-based registry as a key tool to facilitate this work. Our goal is to improve diagnosis, treatment, and quality of life for these patients by the following SPECIFIC AIMS: 1) Develop and expand an international disease registry for patients with PH; 2) Define an expanded metabolic phenotype of PH patients; 3) Employ innovative imaging modalities to more accurately detect and quantify disease progression; 4) Determine if urinary levels of retinol binding protein, a- 1 microglobulin, transforming growth factor (TGF)(31, and v-Glutamyltransferase (GGT) are sensitive markers of ongoing renal damage, can serve as surrogate markers of disease progression, and are reduced by angiotensin blockade; and 5) Application of pharmacogenomics to guide PH treatment. The Registry will allow development of consensus, evidence-based diagnosis and management guidelines. Clinical data, samples, and research protocols completed via the Registry will allow rapid testing of hypotheses and promote worldwide collaboration to advance the care of PH patients.

描述（由申请人提供）：原发性高黄油（pH）是一种罕见的常染色体隐性疾病（估计发病率1：120,000出生）。虽然大多数患者在儿童时期经历了肾上腺素病和/或尿路病的反复发作，但有些患者早在婴儿期就会出现肾衰竭，而其他人则仅作为成年人首次出现尿石症。这种差异的原因在很大程度上是未知的。但是，大多数（如果不是全部）pH患者最终会失去肾功能，并且在大多数情况下也需要肾脏移植。迫切需要确定负责严重疾病表达的因素和有效治疗。这种情况的罕见性使人们了解高黄油和相关肾脏损伤的病理生理学和相关肾脏损伤的发展以及有效治疗的发展。该赠款的总体目的是汇集患者的经验，以识别与pH中疾病进展相关的因素，使用处于危险的患者中的特定治疗策略对其进行修改，并证明肾脏损伤的减少。我们组建了一群独特的医师和科学家，对pH值长期感兴趣。最近，我们开发了一个基于网络的安全注册表，作为促进这项工作的关键工具。我们的目标是通过以下特定目的改善这些患者的诊断，治疗和生活质量：1）针对患有pH的患者开发和扩展国际疾病登记处； 2）定义pH患者的代谢表型扩展； 3）采用创新的成像方式来更准确地检测和量化疾病进展； 4）确定视黄醇结合蛋白，A-1微球蛋白，转化生长因子（TGF）（31和V-lutamylylylysfransferase（GGT）是持续肾脏损伤的敏感标志物，可以用作疾病进展的替代标记物，并通过血管素封闭剂降低药物剂和5）的应用。注册表将允许制定共识，基于证据的诊断和管理指南。通过注册表完成的临床数据，样品和研究方案将允许快速测试假设并促进全球合作，以推动对pH患者的护理。