Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study
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Updated: Apr 16, 2026
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Rachana Shah1, Gregory J Matthews2, Rhia Y Shah3
1Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA.
Insights
Higher levels of Fractalkine (CX3CL1) in chronic kidney disease (CKD) patients are linked to increased risks of cardiovascular disease (CVD) and diabetes. Further research is needed to understand CX3CL1
Area of Science:
- Nephrology
- Cardiology
- Endocrinology
Background:
- Cardiometabolic disease significantly contributes to morbidity and mortality in chronic kidney disease (CKD) patients.
- Fractalkine (CX3CL1) is implicated as a potential mediator in atherosclerosis and metabolic diseases.
- Limited research exists on CX3CL1's association with cardiovascular disease (CVD) events and metabolic traits, especially within the high-risk CKD population.
Purpose of the Study:
- To investigate the relationship between plasma Fractalkine (CX3CL1) levels and cardiometabolic risk factors, prevalent CVD, and incident CVD events in adults with CKD.
- To explore the association of CX3CL1 with diabetes, metabolic syndrome, and insulin resistance in a CKD cohort.
- To determine the prognostic value of CX3CL1 for adverse outcomes including myocardial infarction, all-cause mortality, and a composite outcome in CKD patients.
Main Methods:
- Utilized a cross-sectional and longitudinal observational analysis of adult CKD participants from the Chronic Renal Insufficiency Cohort (CRIC) Study.
- Examined baseline plasma CX3CL1 levels, categorized into quartiles, as the primary predictor.
- Assessed outcomes including estimated glomerular filtration rate (eGFR), prevalent and incident CVD, diabetes, metabolic syndrome, insulin resistance (HOMA-IR), HbA1c, myocardial infarction, all-cause mortality, and a composite endpoint.
Main Results:
- Baseline CX3CL1 levels positively correlated with CVD risk factors, metabolic traits, lower eGFR, and elevated inflammatory cytokines.
- Higher CX3CL1 levels were associated with prevalent CVD (OR, 1.09) and prevalent diabetes (OR, 1.26) after adjustments.
- During a mean 6-year follow-up, a 1-SD increase in CX3CL1 was linked to increased hazards for all-cause mortality (HR, 1.11) and the composite outcome (HR, 1.09) in fully adjusted models.
Conclusions:
- Circulating CX3CL1 may play a role in the pathogenesis of atherosclerotic CVD and diabetes within the CKD population.
- The study's observational design precludes establishing causality or evaluating temporal changes.
- Further research is warranted to elucidate the precise mechanisms by which CX3CL1 influences atherosclerosis and diabetes development in CKD.
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.
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