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Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.
Am J Kidney Dis. 2015 Aug; 66(2):266-73.AJ

Abstract

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.

Authors+Show Affiliations

Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA. Electronic address: shahr@email.chop.edu.School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA.Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.The George Washington University, Washington, DC.National Heart, Lung and Blood Institute, Bethesda, MD.Los Angeles Biomedical Research Institute, Torrance, CA.Medicine, Jesse Brown VA Medical Center and University of Hospital and Health Sciences System, Chicago; Center of Innovation for Complex Chronic Healthcare, Edward Hines Jr VA Hospital, Hines, IL.Division of Research, Kaiser Permanente of Northern California, Oakland, CA.Renal Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia PA.Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Renal Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia PA.School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA.Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. Electronic address: muredach@mail.med.upenn.edu.No affiliation info available

Pub Type(s)

Journal Article
Observational Study
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

25795074

Citation

Shah, Rachana, et al. "Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 66, no. 2, 2015, pp. 266-73.
Shah R, Matthews GJ, Shah RY, et al. Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2015;66(2):266-73.
Shah, R., Matthews, G. J., Shah, R. Y., McLaughlin, C., Chen, J., Wolman, M., Master, S. R., Chai, B., Xie, D., Rader, D. J., Raj, D. S., Mehta, N. N., Budoff, M., Fischer, M. J., Go, A. S., Townsend, R. R., He, J., Kusek, J. W., Feldman, H. I., ... Reilly, M. P. (2015). Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 66(2), 266-73. https://doi.org/10.1053/j.ajkd.2015.01.021
Shah R, et al. Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2015;66(2):266-73. PubMed PMID: 25795074.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: 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 - ,, Y1 - 2015/03/17/ PY - 2014/07/07/received PY - 2015/01/25/accepted PY - 2015/3/22/entrez PY - 2015/3/22/pubmed PY - 2015/10/16/medline KW - Cardiometabolic disease KW - Chronic Renal Insufficiency Cohort KW - atherosclerosis KW - cardiovascular disease (CVD) KW - chronic kidney disease (CKD) KW - diabetes KW - fractalkine (CX3CL1) KW - metabolic syndrome SP - 266 EP - 73 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 66 IS - 2 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. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/25795074/Serum_Fractalkine__CX3CL1__and_Cardiovascular_Outcomes_and_Diabetes:_Findings_From_the_Chronic_Renal_Insufficiency_Cohort__CRIC__Study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(15)00489-8 DB - PRIME DP - Unbound Medicine ER -