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Clinical Journal of The American Society of Nephrology


Background and objectives: Increased serum levels of the acute-phase reactant ceruloplasmin predict adverse clinical outcomes in the setting of acute coronary syndromes and heart failure, but their role in patients with CKD is unclear. This study investigated the relationship of ceruloplasmin with clinical outcomes in CKD, especially with regard to traditional cardiac biomarkers. Design, setting, participants, & measurements: Serum ceruloplasmin levels in consecutive study participants with CKD (n=654; estimated GFR<60 ml/min per 1.73 m2) as well as a control group of non-CKD participants matched for age and sex (n=250) were measured. Study participants were enrolled during 2001–2006 from a population of patients presenting for elective diagnostic coronary angiography and prospectively followed for 3 years (median follow-up=1095 days) to determine incident major adverse cardiac events (defined as a composite of death, nonfatal myocardial infarction, and stroke). Results: Serum ceruloplasmin levels in CKD patients were elevated versus controls (median [interquartile range]; 25.5 [21.8–29.6] versus 22.7 [19.7–26.5] mg/dl; P<0.001) and associated with increased risk of future major adverse cardiac events (hazard ratio, 1.35; 95% confidence interval, 1.0 to 1.82; P=0.04). After adjusting for traditional risk factors, higher serum ceruloplasmin was still associated with higher risk of major adverse cardiac events at 3 years (hazard ratio, 1.61; 95% confidence interval, 1.15 to 2.25; P=0.01). Conclusion: In CKD patients, increased serum ceruloplasmin, a regulator of nitric oxide activity, is associated with increased risk of long-term adverse cardiovascular events, even after multivariable model adjustment for traditional clinical and biologic risk factors.


Support for this research was provided by National Institutes of Health Grant 1R01HL103931. Clinical samples used in this study were from GenBank, a study supported by the National Institutes of Health Grants P01HL076491, P01HL098055, P01HL103453, P20HL113452, and R01HL103866 and the Office of Dietary Supplements, and the Cleveland Clinic Clinical Research Unit of the Case Western Reserve University Clinical and Translational Science Award (UL1TR000439).









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