Serum Fetuin-A Levels Are Associated with Vascular Calcifications and Predict Cardiovascular Events in Renal Transplant Recipients |
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Authors: | Céline Maréchal Georg Schlieper Pauline Nguyen Thilo Krüger Emmanuel Coche Annie Robert Jorgen Floege Eric Goffin Michel Jadoul Olivier Devuyst |
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Affiliation: | *Division of Nephrology and ;†Department of Radiology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain Medical School, Brussels, Belgium; ;‡Division of Nephrology, RWTH University Hospital Aachen, Aachen, Germany; and ;§Department of Epidemiology and biostatistics, Ecole de Santé Publique, Université catholique de Louvain, Brussels, Belgium |
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Abstract: | SummaryBackground and objectivesVascular calcifications predict cardiovascular disease, the major cause of death in renal transplant recipients (RTRs). We studied the determinants of fetuin-A, a potent circulating calcification inhibitor encoded by the AHSG gene, and tested its association with vascular calcifications and long-term survival and cardiovascular events (CVEs) in RTRs.Design, setting, participants, & measurementsTwo hundred seventy-seven prevalent RTRs from a single center were included. CVEs and deaths were prospectively recorded during a 5-year follow-up.ResultsIndependent determinants of lower serum fetuin-A levels were lower plasma cholesterol, the AHSG rs4918 G allele, and history of smoking. Low serum fetuin-A level was a determinant of aortic calcifications (assessed using spiral CT). Low fetuin-A levels (≤0.47 g/L, first quintile) were independently associated with CVEs and deaths (hazard ratio = 1.83; 95% confidence interval, 1.07 to 3.04). The association was confirmed for all-cause mortality, and the major adverse cardiovascular endpoints were analyzed separately. Patients with low fetuin-A and high high-sensitivity C-reactive protein (>4.36 mg/L, fourth quintile) levels had a 3.5-fold increased risk of all-cause mortality and CVEs. In the presence of inflammation, CVE-free survival was influenced by common variants in the AHSG gene.ConclusionsThese data show that low fetuin-A levels are independently associated with aortic calcifications and a higher risk of CVEs and mortality. They support fetuin-A as a circulating biomarker able to identify RTRs at risk for vascular calcifications and CVEs. |
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