Measures of Fibrosis and Clinical Outcomes in Chronic Kidney Disease

慢性肾脏病纤维化和临床结果的测量

• 批准号: 9259967
• 负责人: Amanda Hyre Anderson
• 金额: $ 28.57万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9259967
• 关键词: Adult; Aldosterone; Ancillary Study; Apoptosis; Atherosclerosis; Biological Markers; Cardiovascular Diseases; Cells; Cessation of life; Chronic Kidney Failure; Chronic Kidney Insufficiency; Clinical; Cohort Studies; Complex; Data; Deposition; Disease Progression; End stage renal failure; Event; Extracellular Matrix; Fibroblasts; Fibrosis; Future; Galectin 3; Gelatinase A; Genes; Glomerular Filtration Rate; Growth Factor; Histologic; Hypertension; Hypoxia; Individual; Inflammation; Inflammatory; Injury; Intervention; Investigation; Kidney; Kidney Diseases; Lead; MMP2 gene; Measures; Morbidity - disease rate; Myocardial Infarction; Outcome; Oxidative Stress; Participant; Pathway interactions; Patients; Peptides; Peripheral arterial disease; Process; Procollagen; Proteinuria; Renal function; Research; Resources; Risk; Risk Factors; Sampling; Scientific Inquiry; Stroke; Subgroup; cardiovascular disorder risk; cohort; connective tissue growth factor; disorder risk; fibrogenesis; follow-up; genetic variant; glomerulosclerosis; high risk; high risk population; improved; mortality; novel; novel marker; predict clinical outcome; procollagen Type III-N-terminal peptide; public health relevance

 DESCRIPTION (provided by applicant): The on-going Chronic Renal Insufficiency Cohort (CRIC) Study is comprised of an original cohort of nearly 4,000 US adults with chronic kidney disease (CKD) and aims to elucidate a broad set of risk factors for the high burden of end-stage renal disease (ESRD), cardiovascular disease (CVD) and mortality among those with CKD. Despite kidney fibrosis being a final common pathway for nearly all forms of CKD, the CRIC Study has not yet examined markers of fibrosis as risk factors or predictors of clinical outcomes. The proposed CRIC ancillary study aims to leverage stored samples and accumulated follow-up within the CRIC Study to: 1) investigate the association of fibrosis markers of matrix deposition and inflammation (galectin-3, connective tissue growth factor, matrix metalloproteinase-2, and amino-terminal peptide of procollagen III) with CKD progression defined as ESRD or halving of estimated glomerular filtration rate, 2) determine the relationships between these fibrosis markers and atherosclerotic CVD (myocardial infarction, stroke, and peripheral arterial disease) and death, 3) examine differences in the associations between the fibrosis markers and all outcomes by baseline levels of kidney function and inflammation, and 4) explore associations between genetic variants within the genes encoding for the measured fibrosis markers and CKD progression. Elevations in one or more of these fibrosis markers early in CKD could help identify a high-risk subgroup that may benefit most from more intensive risk factor management and suppression of inflammation, and potentially lead to targets for novel interventions for patients with CKD.

 描述（由申请人提供）：正在进行的慢性肾功能不全队列 (CRIC) 研究由近 4,000 名患有慢性肾病 (CKD) 的美国成年人组成，旨在阐明导致高肾功能不全的一系列广泛风险因素。尽管肾纤维化是几乎所有形式的最终共同途径，但终末期肾病 (ESRD)、心血管疾病 (CVD) 和 CKD 患者的死亡率仍然受到影响。 CKD、CRIC 研究尚未将纤维化标志物作为危险因素或临床结果的预测因子进行研究。拟议的 CRIC 辅助研究旨在利用 CRIC 研究中存储的样本和累积的随访数据来：1）调查纤维化标志物的关联。基质沉积和炎症（半乳糖凝集素 3、结缔组织生长因子、基质金属蛋白酶 2 和前胶原 III 的氨基末端肽）与 CKD 进展（定义为 ESRD 或减半）的关系估计肾小球滤过率，2) 确定这些纤维化标志物与动脉粥样硬化 CVD（心肌梗死、中风和外周动脉疾病）和死亡之间的关系，3) 通过基线水平检查纤维化标志物与所有结果之间关联的差异肾功能和炎症，4) 探索编码所测量的纤维化标志物的基因内的遗传变异与这些纤维化标志物中的一种或多种的 CKD 进展之间的关联。 CKD 早期的监测可以帮助识别一个高风险亚组，该亚组可能从更强化的危险因素管理和炎症抑制中获益最多，并有可能为 CKD 患者制定新的干预措施目标。