Measures of Fibrosis and Clinical Outcomes in Chronic Kidney Disease

 描述（由申请方提供）：正在进行的慢性肾功能不全队列（CRIC）研究由近4，000名美国慢性肾脏疾病（CKD）成人的原始队列组成，旨在阐明CKD患者中终末期肾脏疾病（ESRD）、心血管疾病（CVD）和死亡率高负担的一系列广泛风险因素。尽管肾纤维化是几乎所有形式CKD的最终共同途径，但CRIC研究尚未将纤维化标志物作为风险因素或临床结局的预测因子进行研究。拟议的审评委辅助研究旨在利用审评委研究中储存的样本和累积的后续行动，以便：1）研究基质沉积和炎症的纤维化标志物的关联（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的氨基端肽）伴CKD进展（定义为ESRD或估计肾小球滤过率减半），2）确定这些纤维化标志物与动脉粥样硬化性CVD之间的关系（心肌梗塞、中风和外周动脉疾病）和死亡，3）通过肾功能和炎症的基线水平检查纤维化标志物和所有结果之间的关联的差异，和4）探索编码测量的纤维化标志物的基因内的遗传变异体与CKD进展之间的关联。CKD早期一种或多种纤维化标志物的升高可能有助于识别一个高风险亚组，该亚组可能从更密集的风险因素管理和炎症抑制中获益最多，并可能为CKD患者提供新的干预措施。

 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.