title: Serum fetuin-A levels are associated with vascular calcifications and predict cardiovascular events in renal transplant recipients.
abstract: OBJECTIVE
  Vascular 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.
  
  
  METHODS
  Two hundred seventy-seven prevalent RTRs from a single center were included. CVEs and deaths were prospectively recorded during a 5-year follow-up.
  
  
  RESULTS
  Independent 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Division of Nephrology, Cliniques Universitaires Saint-Luc, UCL Medical School, 10 Avenue Hippocrate, B-1200 Brussels, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Maréchal
authors.forename: Georg
authors.initials: G
authors.lastname: Schlieper
authors.forename: Pauline
authors.initials: P
authors.lastname: Nguyen
authors.forename: Thilo
authors.initials: T
authors.lastname: Krüger
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Coche
authors.forename: Annie
authors.initials: A
authors.lastname: Robert
authors.forename: Jorgen
authors.initials: J
authors.lastname: Floege
authors.forename: Eric
authors.initials: E
authors.lastname: Goffin
authors.forename: Michel
authors.initials: M
authors.lastname: Jadoul
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
mesh_terms: D000328:Adult; D001018:Aortic Diseases / Q000097:blood / Q000235:genetics / Q000401:mortality*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism*; D002114:Calcinosis / Q000097:blood / Q000235:genetics / Q000401:mortality*; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000401:mortality*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D060749:alpha-2-HS-Glycoprotein
chemical_list: C556354:AHSG protein, human; D015415:Biomarkers; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein; D002784:Cholesterol