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Updated: Mar 19, 2026
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD
Jia Sun1, Jonas Axelsson2, Anna Machowska1
1Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology and.
Insights
Interleukin-6 (IL-6) is a strong predictor of cardiovascular disease (CVD) and mortality in patients with stage 5 chronic kidney disease (CKD). Elevated IL-6 levels independently identify patients at high risk for CVD and death.
Area of Science:
- Nephrology
- Cardiology
- Biomarker Discovery
Background:
- Patients with chronic kidney disease (CKD) face a high risk of cardiovascular disease (CVD) and premature death.
- Numerous circulating biomarkers are elevated in CKD, but their predictive value for CVD and mortality is not fully understood.
Purpose of the Study:
- To compare the predictive strength of 12 different biomarkers for clinically overt CVD and all-cause mortality in patients with stage 5 CKD.
- To identify which biomarkers independently predict CVD and mortality in this high-risk population.
Main Methods:
- A cohort of 543 patients with stage 5 CKD undergoing dialysis were analyzed.
- Levels of 12 biomarkers (including albumin, hsCRP, IGF-1, IL-6, TnT, TNF, sVCAM-1, and WBC) were measured.
- Predictive values for baseline CVD, protein-energy wasting (PEW), and all-cause mortality were assessed using receiver operating characteristic analysis and regression models.
Main Results:
- Most biomarkers were elevated in CKD patients, with higher levels in those with CVD.
- Age, IL-6, troponin T (TnT), high-sensitivity C-reactive protein (hsCRP), and IGF-1 predicted baseline CVD and mortality.
- Independently, IL-6, soluble vascular cellular adhesion molecule 1 (sVCAM-1), and albumin predicted CVD, while IL-6, white blood cell (WBC) count, and TNF predicted all-cause mortality.
Conclusions:
- Interleukin-6 (IL-6) is a robust classifier of clinically overt CVD and a significant predictor of all-cause mortality in stage 5 CKD patients.
- IL-6, sVCAM-1, and albumin are key independent predictors of CVD, while IL-6, WBC, and TNF are independent predictors of mortality in this population.
Background And Objectives:
The high risk of cardiovascular disease (CVD) and premature death in patients with CKD associates with a plethora of elevated circulating biomarkers that may reflect distinct signaling pathways or simply, are epiphenomena of CKD. We compared the predictive strength of 12 biomarkers analyzed concomitantly in patients with stage 5 CKD.
Design, Setting, Participants, & Measurements:
From 1994 to 2014, 543 patients with stage 5 CKD (median age =56 years old; 63% men; 199 patients had CVD) took part in our study on malnutrition, inflammation, and CVD in incident dialysis patients. Circulating levels of albumin, ferritin, high-sensitivity C-reactive protein (hsCRP), IGF-1, IL-6, orosomucoid, troponin T (TnT), TNF, soluble intracellular adhesion molecule, soluble vascular cellular adhesion molecule 1 (sVCAM-1), and platelet and white blood cell (WBC) counts were analyzed as predictors of the presence of clinically overt CVD at baseline, protein-energy wasting (PEW), and subsequent all-cause mortality. During follow-up for a median of 28 months, there were 149 deaths, 81 of which were caused by CVD.
Results:
Most biomarkers were elevated compared with reference values and--except for albumin, ferritin, and IGF-1-higher in patients with CVD. In receiver operating characteristic analysis, age, IL-6, TnT, hsCRP, and IGF-1 were classifiers of baseline CVD and predictors of all-cause mortality. In addition to age, diabetes mellitus, smoking (for CVD), and PEW, only IL-6, relative risk (RR) 1.10 and 95% confidence interval ([95% CI], 1.02 to 1.19), sVCAM-1 RR 1.09 (95% CI, 1.01 to 1.17), and serum albumin RR 0.89 (95% CI, 0.83 to 0.95) associated with baseline CVD, and only WBC, hazard ratio (HR) 1.94 (95% CI, 1.34 to 2.82), IL-6 HR 1.79 (95% CI, 1.20 to 2.67), and TNF HR 0.65 (95% CI, 0.44 to 0.97) predicted all-cause mortality.
Conclusions:
In addition to age and comorbidities, only IL-6, sVCAM-1, and albumin could-independently of other biomarkers-classify clinical CVD, and only IL-6, WBC, and TNF could-independently of other biomarkers-predict all-cause mortality risk. These data underscore the robustness of IL-6 as a classifier of clinically overt CVD and predictor of all-cause mortality in patients with stage 5 CKD.
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