Prevention of Renal Damage in Primary Hyperoxaluria

原发性高草酸尿症肾损伤的预防

基本信息

批准号：
7270069
负责人：
Dawn Schmautz Milliner
金额：
$ 44.42万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
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/7270069
关键词：
Adult Angiotensins Birth Blood Calcium Oxalate Calculi Caring Cell Line Cells Characteristics Childhood Chronic Kidney Failure Clinical Clinical Data Clinical Trials Collaborations Communities Condition Consensus Development Data Databases Deposition Development Diagnosis Dialysis procedure Disease Disease Progression End stage renal failure Environmental Risk Factor Excretory function Filtration Fostering Functional disorder Future Gamma-glutamyl transferase Genotype Glycolates Glyoxylates Goals Grant Guidelines Hyperoxaluria Image Incidence Individual Inflammation Inherited Injury Inpatients International Intervention Kidney Kidney Diseases Kidney Failure Kidney Transplantation Laboratories Leukocytes Lithiasis Liver Longitudinal Studies Lymphocyte Metabolic Methods Modality Molecular Chaperones Mononuclear Mutation Nephrocalcinosis Nephrolithiasis Online Systems Outcome Oxalates Patients Pharmacogenomics Phenotype Physical Dialysis Physicians Prevention Primary Health Care Primary Hyperoxaluria Process Protocols documentation Quality of life Range Rate Registries Renal Interstitial Cell Renal Replacement Therapy Renal function Research Research Design Retinol Binding Proteins Risk Sampling Scientist Score Secure Severity of illness Siblings Staging Surrogate Markers Technology Testing Therapeutic Agents Tissue Sample Tissues Transforming Growth Factors Treatment Efficacy Tubular formation Urine Work base burden of illness calcification cohort disease registry evidence based guidelines experience follow-up glutamyltransferase glycolate glyoxylate improved indexing infancy innovation interest liver transplantation oxalosis patient registry patient/disease registry pyridoxine repository response tool treatment trial urinary urolithiasis

项目摘要

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）：原发性高草酸尿症 (PH) 是一种罕见的常染色体隐性遗传疾病（估计发病率为 1:120,000 新生儿）。虽然大多数患者在儿童时期经历肾钙质沉着症和/或尿石症反复发作，但有些患者早在婴儿期就出现肾功能衰竭，而另一些患者则在成年时仅出现尿石症。造成这种差异的原因很大程度上尚不清楚。然而，大多数（如果不是全部）PH 患者最终会丧失肾功能，需要进行肾移植，大多数情况下还需要进行肝移植。迫切需要确定导致严重疾病表现的因素并寻求有效的治疗方法。由于这种情况的罕见性，对高草酸尿症和相关肾损伤的病理生理学的了解以及有效治疗方法的开发进展缓慢。该资助的总体目标是汇集患者经验，以确定与 PH 疾病进展相关的因素，对有风险的患者使用特定的治疗策略进行修改，并证明肾损伤的减少。我们组建了一个独特的团队，由对 PH 长期感兴趣的医生和科学家组成。最近，我们开发了一个安全的、基于网络的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具体目标来改善这些患者的诊断、治疗和生活质量： 1) 开发和扩大 PH 患者的国际疾病登记； 2) 定义PH患者的扩展代谢表型； 3) 采用创新的成像方式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-谷氨酰转移酶 (GGT) 的尿液水平是否是持续性肾损伤的敏感标志物，是否可以作为疾病进展的替代标志物，以及血管紧张素阻断可减少；5) 应用药物基因组学指导 PH 治疗。登记处将允许制定共识、循证诊断和管理指南。通过注册中心完成的临床数据、样本和研究方案将允许快速检验假设并促进全球合作，以促进PH患者的护理。