title: Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.
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.
  
  
  METHODS
  Cross-sectional and longitudinal observational analysis.
  
  
  METHODS
  Adults with CKD from 7 US sites participating in the Chronic Renal Insufficiency Cohort (CRIC) Study.
  
  
  METHODS
  Quartiles of plasma CX3CL1 levels at baseline.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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: Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA. Electronic address: shahr@email.chop.edu.
authors: Rachana
authors: R
authors: Shah
authors: School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA.
authors: Gregory J
authors: GJ
authors: Matthews
authors: Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Rhia Y
authors: RY
authors: Shah
authors: Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.
authors: Catherine
authors: C
authors: McLaughlin
authors: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
authors: Jing
authors: J
authors: Chen
authors: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Melanie
authors: M
authors: Wolman
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Stephen R
authors: SR
authors: Master
authors: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Boyang
authors: B
authors: Chai
authors: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Dawei
authors: D
authors: Xie
authors: Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Daniel J
authors: DJ
authors: Rader
authors: The George Washington University, Washington, DC.
authors: Dominic S
authors: DS
authors: Raj
authors: National Heart, Lung and Blood Institute, Bethesda, MD.
authors: Nehal N
authors: NN
authors: Mehta
authors: Los Angeles Biomedical Research Institute, Torrance, CA.
authors: Matthew
authors: M
authors: Budoff
authors: 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.
authors: Michael J
authors: MJ
authors: Fischer
authors: Division of Research, Kaiser Permanente of Northern California, Oakland, CA.
authors: Alan S
authors: AS
authors: Go
authors: Renal Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia PA.
authors: Raymond R
authors: RR
authors: Townsend
authors: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
authors: Jiang
authors: J
authors: He
authors: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
authors: John W
authors: JW
authors: Kusek
authors: 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.
authors: Harold I
authors: HI
authors: Feldman
authors: School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA.
authors: Andrea S
authors: AS
authors: Foulkes
authors: Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. Electronic address: muredach@mail.med.upenn.edu.
authors: Muredach P
authors: MP
authors: Reilly
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology; D054428:Chemokine CX3CL1 / Q000097:blood*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000097:blood* / Q000453:epidemiology; D005260:Female; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000453:epidemiology; D008875:Middle Aged; D009026:Mortality; D009203:Myocardial Infarction / Q000097:blood* / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000453:epidemiology; D012307:Risk Factors
chemical_list: C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1
keywords: Cardiometabolic disease; Chronic Renal Insufficiency Cohort; atherosclerosis; cardiovascular disease (CVD); chronic kidney disease (CKD); diabetes; fractalkine (CX3CL1); metabolic syndrome