Measures of Fibrosis and Clinical Outcomes in Chronic Kidney Disease

 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名患有慢性肾脏疾病(CKD)的美国成年人组成，旨在阐明导致终末期肾脏疾病(ESRD)、心血管疾病(CVD)和CKD患者死亡率高负担的广泛风险因素。尽管肾脏纤维化是几乎所有形式CKD的最终共同途径，但CRIC的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素。拟议的CRIC辅助研究旨在利用CRIC研究中储存的样本和累积的随访来：1)调查基质沉积和炎症的纤维化标记物(Galectin-3、结缔组织生长因子、基质金属蛋白酶-2和III型前胶原氨基端肽)与CKD进展(定义为终末期肾病或估计的肾小球滤过率减半)的关系；2)确定这些纤维化标记物与动脉粥样硬化性心血管疾病(心肌梗死、中风和外周动脉疾病)和死亡的关系；3)通过肾功能和炎症的基线水平检查纤维化标记物和所有预后之间的差异。以及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CKD进展之间的关联。CKD早期一个或多个纤维化标志物的升高可能有助于识别可能从更密集的风险因素管理和炎症抑制中受益最大的高危亚组，并可能导致CKD患者的新干预措施的靶点。

 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.