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.
Despite kidney fibrosis being a final common pathway for nearly all forms of chronic kidney disease (CKD), little is known about markers of fibrosis as risk factors or predictors of clinical outcomes. The proposed CRIC ancillary study aims to investigate the association of four fibrosis markers with the outcomes of CKD progression, atherosclerotic cardiovascular disease, and mortality in the setting of CKD. 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.
