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Observational Study
. 2015 Aug;66(2):266-73.
doi: 10.1053/j.ajkd.2015.01.021. Epub 2015 Mar 17.

Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Rachana Shah  1 , Gregory J Matthews  2 , Rhia Y Shah  3 , Catherine McLaughlin  4 , Jing Chen  5 , Melanie Wolman  6 , Stephen R Master  7 , Boyang Chai  6 , Dawei Xie  6 , Daniel J Rader  3 , Dominic S Raj  8 , Nehal N Mehta  9 , Matthew Budoff  10 , Michael J Fischer  11 , Alan S Go  12 , Raymond R Townsend  13 , Jiang He  5 , John W Kusek  14 , Harold I Feldman  15 , Andrea S Foulkes  2 , Muredach P Reilly  16 ; CRIC Study Investigators
Collaborators, Affiliations
Observational Study

Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Rachana Shah et al. Am J Kidney Dis. 2015 Aug.

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.

Keywords: Cardiometabolic disease; Chronic Renal Insufficiency Cohort; atherosclerosis; cardiovascular disease (CVD); chronic kidney disease (CKD); diabetes; fractalkine (CX3CL1); metabolic syndrome.

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Figures

Figure 1
Figure 1
Adjusted survival curves for effect of plasma CX3CL1 (fractalkine) quartiles on incident events. Fully adjusted for A) probable and definite MI, B) all-cause mortality, and C) composite probable and definite MI / all-cause mortality.
See this image and copyright information in PMC

Comment in

References

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