TY - JOUR
T1 - Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes
T2 - Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study
AU - Shah, Rachana
AU - Matthews, Gregory J.
AU - Shah, Rhia Y.
AU - McLaughlin, Catherine
AU - Chen, Jing
AU - Wolman, Melanie
AU - Master, Stephen R.
AU - Chai, Boyang
AU - Xie, Dawei
AU - Rader, Daniel J.
AU - Raj, Dominic S.
AU - Mehta, Nehal N.
AU - Budoff, Matthew
AU - Fischer, Michael J.
AU - Go, Alan S.
AU - Townsend, Raymond R.
AU - He, Jiang
AU - Kusek, John W.
AU - Feldman, Harold I.
AU - Foulkes, Andrea S.
AU - Reilly, Muredach P.
AU - Appel, Lawrence J.
AU - Lash, James P.
AU - Ojo, Akinlolu
AU - Rahman, Mahboob
N1 - Funding Information:
Support: This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health (NIH; R01-DK071224 and R01-DK090505 to Mr Reilly, K23-DK095913 to Dr Shah, K24-DK002651 to Dr Feldman). The National Heart, Lung and Blood Institute of the NIH also provided support ( R01-HL107196 to Dr Foulkes and K24-HL107643 , U01-HL108636 , and R01-HL113147 to Mr Reilly). The US Department of Veterans Affairs Health Services Research and Development Service Award supports Dr Fischer. Dr Mehta is supported by NIH Intramural Award [HL-Z0000]. Funding for the CRIC Study was obtained under a cooperative agreement from the NIDDK ( U01DK060990 , U01DK060984 , U01DK061022 , U01DK061021 , U01DK061028 , U01DK060980 , U01DK060963 , and U01DK060902 ). In addition, this work was supported in part by the following: the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award (CTSA) NIH/National Center for Advancing Translational Sciences (NCATS) UL1TR000003 , Johns Hopkins University UL1 TR-000424 , University of Maryland GCRC M01 RR-16500 , Clinical and Translational Science Collaborative of Cleveland , UL1TR000439 from the NCATS component of the NIH and NIH Roadmap for Medical Research , Michigan Institute for Clinical and Health Research (MICHR) UL1TR000433 , University of Illinois at Chicago CTSA UL1RR029879 , Tulane University Translational Research in Hypertension and Renal Biology P30GM103337 , and Kaiser Permanente NIH/National Center for Research Resources UCSF-CTSI UL1 RR-024131 .
Publisher Copyright:
© 2015 National Kidney Foundation, Inc.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Background Cardiometabolic disease is a major cause of morbidity and mortality in persons with chronic kidney disease (CKD). Fractalkine (CX3CL1) is a potential mediator of both atherosclerosis and metabolic disease. Studies of the relationship of CX3CL1 with risk of cardiovascular disease (CVD) events and metabolic traits are lacking, particularly in the high-risk setting of CKD. Study Design Cross-sectional and longitudinal observational analysis. Setting & Participants Adults with CKD from 7 US sites participating in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictor Quartiles of plasma CX3CL1 levels at baseline. Outcomes Baseline estimated glomerular filtration rate from a creatinine and cystatin C-based equation, prevalent and incident CVD, diabetes, metabolic syndrome and its criteria, homeostatic model assessment of insulin resistance, hemoglobin A1c level, myocardial infarction, all-cause mortality, and the composite outcome of myocardial infarction/all-cause mortality. Results Among 3,687 participants, baseline CX3CL1 levels were associated positively with several CVD risk factors and metabolic traits, lower estimated glomerular filtration rate, and higher levels of inflammatory cytokines, as well as prevalent CVD (OR, 1.09; 95% CI, 1.01-1.19; P = 0.03). Higher CX3CL1 level also was associated with prevalent diabetes (OR, 1.26; 95% CI, 1.16-1.38; P < 0.001) in adjusted models. During a mean follow-up of 6 years, there were 352 deaths, 176 myocardial infarctions, and 484 composite outcomes. In fully adjusted models, 1-SD higher CX3CL1 level increased the hazard for all-cause mortality (1.11; 95% CI, 1.00-1.22; P = 0.02) and the composite outcome (1.09; 95% CI, 1.00-1.19; P = 0.04). Limitations Study design did not allow evaluation of changes over time, correlation with progression of phenotypes, or determination of causality of effect. Conclusions Circulating CX3CL1 level may contribute to both atherosclerotic CVD and diabetes in a CKD cohort. Further studies are required to establish mechanisms through which CX3CL1 affects the pathogenesis of atherosclerosis and diabetes.
AB - Background Cardiometabolic disease is a major cause of morbidity and mortality in persons with chronic kidney disease (CKD). Fractalkine (CX3CL1) is a potential mediator of both atherosclerosis and metabolic disease. Studies of the relationship of CX3CL1 with risk of cardiovascular disease (CVD) events and metabolic traits are lacking, particularly in the high-risk setting of CKD. Study Design Cross-sectional and longitudinal observational analysis. Setting & Participants Adults with CKD from 7 US sites participating in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictor Quartiles of plasma CX3CL1 levels at baseline. Outcomes Baseline estimated glomerular filtration rate from a creatinine and cystatin C-based equation, prevalent and incident CVD, diabetes, metabolic syndrome and its criteria, homeostatic model assessment of insulin resistance, hemoglobin A1c level, myocardial infarction, all-cause mortality, and the composite outcome of myocardial infarction/all-cause mortality. Results Among 3,687 participants, baseline CX3CL1 levels were associated positively with several CVD risk factors and metabolic traits, lower estimated glomerular filtration rate, and higher levels of inflammatory cytokines, as well as prevalent CVD (OR, 1.09; 95% CI, 1.01-1.19; P = 0.03). Higher CX3CL1 level also was associated with prevalent diabetes (OR, 1.26; 95% CI, 1.16-1.38; P < 0.001) in adjusted models. During a mean follow-up of 6 years, there were 352 deaths, 176 myocardial infarctions, and 484 composite outcomes. In fully adjusted models, 1-SD higher CX3CL1 level increased the hazard for all-cause mortality (1.11; 95% CI, 1.00-1.22; P = 0.02) and the composite outcome (1.09; 95% CI, 1.00-1.19; P = 0.04). Limitations Study design did not allow evaluation of changes over time, correlation with progression of phenotypes, or determination of causality of effect. Conclusions Circulating CX3CL1 level may contribute to both atherosclerotic CVD and diabetes in a CKD cohort. Further studies are required to establish mechanisms through which CX3CL1 affects the pathogenesis of atherosclerosis and diabetes.
KW - Chronic Renal Insufficiency Cohort
KW - Index Words Cardiometabolic disease
KW - atherosclerosis
KW - cardiovascular disease (CVD)
KW - chronic kidney disease (CKD)
KW - diabetes
KW - fractalkine (CX3CL1)
KW - metabolic syndrome
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U2 - 10.1053/j.ajkd.2015.01.021
DO - 10.1053/j.ajkd.2015.01.021
M3 - Article
C2 - 25795074
AN - SCOPUS:84937967994
SN - 0272-6386
VL - 66
SP - 266
EP - 273
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 2
ER -