Chronic Kidney Disease Biomarkers Consortium (CKD BioCon) U01

慢性肾脏病生物标志物联盟 (CKD BioCon) U01

• 批准号: 9561893
• 负责人: Michelle Denburg
• 金额: $ 20万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-14 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9561893
• 关键词: 16 year old; Acute Appendicitis; Adult; Age; Area Under Curve; Arterial Disorder; Biological Assay; Biological Markers; Blood; Blood Pressure; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Child; Childhood; Chronic Kidney Failure; Cohort Studies; Collection; Comorbidity; Data; Diabetes Mellitus; Diagnosis; Direct Repeats; Discrimination; Disease; End stage renal failure; Enrollment; Event; Filtration; Fractionation; Functional disorder; Gender; General Population; Glomerular Filtration Rate; Growth and Development function; Health; Hypertension; Individual; Infant; Ions; Kidney; Kidney Diseases; Kidney Failure; Laboratories; Left Ventricular Hypertrophy; Life Expectancy; Liquid Chromatography; Mass Spectrum Analysis; Measurement; Medical; Metabolic Bone Diseases; Methods; Mucocutaneous Lymph Node Syndrome; Nature; Nested Case-Control Study; Outcome; Participant; Phenotype; Physicians; Plasma; Population; Preventive; Proteins; Proteinuria; Proteome; Proteomics; Publishing; Race; Receiver Operating Characteristics; Recording of previous events; Renal Replacement Therapy; Renal function; Renal glomerular disease; Reporting; Risk; Risk Factors; Sampling; Secondary to; Serum; Techniques; Therapeutic Intervention; Time; Urinary tract; Urine; Validation; Work; base; biobank; biomarker discovery; biomarker validation; candidate marker; cardiovascular disorder risk; clinical application; clinical predictors; cohort; comparative; congenital anomaly; coronary artery calcification; early onset; follow-up; human disease; interest; longitudinal analysis; male; mass spectrometer; mortality; new therapeutic target; novel; novel marker; peer; prevent; progression marker; public health relevance; response; specific biomarkers; tandem mass spectrometry; targeted treatment; urinary; young adult

 DESCRIPTION (provided by applicant): When children have kidney dysfunction, their decline is more rapid than adults, and they develop many other complicating medical conditions that threaten their life expectancy. The majority of young adults with a history of kidney failure in childhood suffer significant comorbidities, with as much as a 10- to 100-fold increased risk of cardiovascular disease and 30- to 150-fold higher mortality compared to their age matched peers. The ability of physicians to identify when kidney function decline accelerates or the early onset of cardiovascular disease is currently limited. Recent advances in the laboratory techniques available to study the nature and variety of urine proteins (urine proteomics) have led to the discovery of highly discriminant biomarkers of varied diseases, and also suggested new potential targets for therapy. However, these techniques have not been applied to study progression of chronic kidney disease (CKD) in children. Analysis of urine has several advantages over blood serum or plasma: urine can be obtained easily and in much larger volumes. Also, urine sampling can be frequent and repeated. As urine is a filtrate of serum, it has a comparatively simpler composition. This proposal, in response to RFA-DK-14-011 for the Chronic Kidney Disease Biomarkers Consortium (CKD BioCon) (U01), proposes to utilize recent advances in state-of-the-art urine proteomic profiling as well as the comprehensive careful characterization of and collection of biosamples from children with CKD in the Chronic Kidney Disease in Children (CKiD) cohort over the last decade, to perform the first large-scale discovery and validation of novel urinary biomarkers of CKD progression in children.

 描述（由申请人提供）：当儿童患有肾功能障碍时，其肾功能下降速度比成人更快，并且会出现许多其他复杂的医疗状况，威胁其预期寿命。大多数有肾衰竭病史的年轻人都患有严重的合并症，与同龄人相比，患心血管疾病的风险高出 10 至 100 倍，死亡率高出 30 至 150 倍。目前，医生识别肾功能何时加速衰退或心血管疾病何时提前发作的能力有限。可用于研究尿蛋白性质和多样性（尿液蛋白质组学）的实验室技术的最新进展导致发现了各种疾病的高度区分性生物标志物，并提出了新的潜在治疗靶点。然而，这些技术尚未应用于研究儿童慢性肾脏病（CKD）的进展。与血清或血浆相比，尿液分析有几个优点：可以轻松获得更大体积的尿液。此外，尿液取样可以频繁且重复。由于尿液是血清的滤液，其成分相对简单。该提案是为了响应慢性肾脏病生物标志物联盟 (CKD BioCon) (U01) 的 RFA-DK-14-011，建议利用最先进的尿液蛋白质组分析的最新进展以及过去十年对儿童慢性肾脏病 (CKiD) 队列中 CKD 儿童生物样本的全面仔细表征和收集，以执行第一个 大规模发现和验证儿童 CKD 进展的新型尿液生物标志物。