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Updated: Jul 13, 2026
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Searching for biomarker patterns characterizing carotid atherosclerotic burden in patients with reduced renal
Francesco Addabbo1, Francesca Mallamaci, Daniela Leonardis
1Department of Medicine, Renal Research Institute, New York Medical College, Valhalla, NY, USA.
Insights
Chronic kidney disease (CKD) patients have increased cardiovascular risk. Biomarkers like Interleukin-6 (IL-6) strongly correlate with carotid atherosclerosis severity in CKD.
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Biomarker Discovery
Background:
- Chronic kidney disease (CKD) is strongly linked to increased cardiovascular (CV) complications.
- Assessing vascular endothelial function and biomarkers can refine CV risk assessment in CKD patients.
Purpose of the Study:
- To analyze the relationship between various biomarkers and atherosclerotic burden in CKD patients.
- To identify specific biomarkers that predict the severity of carotid atherosclerosis in individuals with CKD.
Main Methods:
- Multiplexed analysis of 16 biomarkers in 75 CKD patients and 33 controls.
- Carotid artery echo-Doppler studies to assess intima-media thickness and plaque presence.
- Principal component analysis to derive a composite atherosclerosis severity score.
Main Results:
- A composite atherosclerosis score explained 68% of the variance in carotid atherosclerosis.
- Interleukin-6 (IL-6), Matrix Metalloproteinase 9 (MMP9), Plasminogen activator inhibitor-1 (t-PAI-1), and Vascular Endothelial Growth Factor (VEGF) correlated with atherosclerosis severity.
- IL-6 was the strongest independent predictor of atherosclerosis severity in multivariate analysis.
Conclusions:
- Multiplexed biomarker screening effectively identifies markers associated with carotid atherosclerosis in CKD.
- IL-6, MMP-9, t-PAI-1, and VEGF are significantly correlated with carotid atherosclerotic burden in CKD patients.
- These findings highlight potential targets for improved CV risk stratification in CKD.
Background:
Evidence linking chronic kidney disease (CKD) with the increased risk of cardiovascular (CV) complications is firm. It is becoming clear that testing functions of the vascular endothelium in conjunction with various biomarkers may better the definition of CV risk profile in CKD patients.
Methods:
Using Multiplexed analysis of 16 markers reflecting pro-inflammatory, anti-inflammatory, angiogenic, metabolic and anti-fibrinolytic factors in a series of 75 patients with CKD, who underwent echo-coloured Doppler study of carotid arteries, we analysed the contribution of each parameter to the characterization of atherosclerotic burden. As control group we enrolled 33 healthy individuals.
Results:
On univariate analysis, intima-media thickness, number of atherosclerotic plaques and internal diameter of carotid arteries were strongly interrelated. Starting with these indicators of carotid atherosclerosis, we extracted by principal component analysis a single composite atherosclerosis severity score that accounted for 68% of the total variance of original variables. Biomarkers significantly related to severity of carotid atherosclerosis were MMP9, t-PAI-1, IL-6, NT-proBNP, IL-8 and VEGF. In multiple linear regression models adjusting for clinical variables the gain in prediction power was achieved when we added MMP9 and t-PAI-1 to the basic model. IL-6 produced the highest increase in the multiple R2 of the basic model. The combination of MMP9, t-PAI-1, IL-6, NT-proBNP, IL-8 and VEGF added to the basic model achieved gain in prediction power of + 7.5%. In this expanded model, IL-6 was the only biomarker that significantly predicted the severity of atherosclerosis.
Conclusion:
Multiplexed screening revealed that IL-6, MMP-9, tPAI-1 and VEGF showed a tight correlation with carotid atherosclerotic burden in patients with CKD.
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