Chronic Kidney Disease Biomarkers Consortium (CKD BioCon) U01

 描述(申请人提供)：当儿童有肾功能障碍时，他们的衰退比成年人更快，他们会发展成许多其他复杂的疾病，威胁他们的预期寿命。大多数在童年时有肾衰竭病史的年轻人都患有严重的合并症，与同龄的同龄人相比，患心血管疾病的风险增加了10到100倍，死亡率增加了30到150倍。目前，医生识别肾功能衰退加速或心血管疾病早期发作的能力有限。可用于研究尿蛋白性质和多样性的实验室技术(尿蛋白组学)的最新进展导致了对各种疾病的高度区分的生物标志物的发现，并提出了新的潜在治疗目标。然而，这些技术还没有被应用于研究儿童慢性肾脏疾病(CKD)的进展。与血清或血浆相比，尿液分析有几个优点：尿液可以很容易地获得，而且体积要大得多。此外，尿液采样可能会频繁和重复。因为尿液是血清的滤液，所以它的成分相对简单。针对RFA-DK-14-011 for the CKD Biomarkers Consortium(CKD Biocon)(U01)，这项建议建议利用最新的尿蛋白组学研究进展，以及过去十年来对CKD儿童慢性肾脏疾病(CKiD)队列中CKD儿童生物样本的全面仔细表征和收集，以进行首次大规模发现和验证儿童CKD进展的新尿路生物标志物。

 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.