BACKGROUND: Vascular calcification independently predicts cardiovascular disease, the major cause of death in kidney transplant recipients (KTRs). Longitudinal studies of vascular calcification in KTRs are few and small and have short follow-up. We assessed the evolution of coronary artery (CAC) and thoracic aorta calcification and their determinants in a cohort of prevalent KTRs. STUDY DESIGN: Longitudinal. SETTING PARTICIPANTS: The Agatston score of coronary arteries and thoracic aorta was measured by 16-slice spiral computed tomography in 281 KTRs. PREDICTORS: Demographic, clinical, and biochemical parameters were recorded simultaneously. OUTCOMES MEASUREMENTS: The Agatston score was measured again 3.5 or more years later. RESULTS: Repeated analyzable computed tomographic scans were available for 197 (70%) KTRs after 4.40 ± 0.28 years; they were not available for the rest of patients because of death (n = 40), atrial fibrillation (n = 1), other arrhythmias (n = 4), refusal (n = 35), or technical problems precluding confident calcium scoring (n = 4). CAC and aorta calcification scores increased significantly (by a median of 11% and 4% per year, respectively) during follow-up. By multivariable linear regression, higher baseline CAC score, history of cardiovascular event, use of a statin, and lower 25-hydroxyvitamin D(3) level were independent determinants of CAC progression. Independent determinants of aorta calcification progression were higher baseline aorta calcification score, higher pulse pressure, use of a statin, older age, higher serum phosphate level, use of aspirin, and male sex. Significant regression of CAC or aorta calcification was not observed in this cohort. LIMITATIONS: Cohort of prevalent KTRs with potential survival bias; few patients with diabetes and nonwhites, limiting the generalizability of results. CONCLUSION: In contrast to previous small short-term studies, we show that vascular calcification progression is substantial within 4 years in prevalent KTRs and is associated with several traditional and nontraditional cardiovascular risk factors, some of which are modifiable.

SummaryBackground and objectives 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 longterm survival and cardiovascular events (CVEs) in RTRs.Design, setting, participants, & measurements 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 (Յ0.47 g/L, first quintile) were independently associated with CVEs and deaths (hazard ratio ϭ 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 (Ͼ4.36 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.

Our study shows for the first time that CAC is a strong independent predictor of CVE in RTR.

Background: Coronary artery calcifications independently predict cardiovascular events (CVE) in the general population. We assessed the prevalence and determinants of coronary (CAC) and thoracic aorta (AoC) calcifications in renal transplant recipients (RTR). Methods: Consecutive RTR living in Belgium, with an isolated kidney graft functioning for more than 1 year, were asked to participate. They underwent a 16-slice spiral computerized tomography in order to measure calcium mass. Demographic, clinical, biochemical and urinary parameters were recorded. Results: We included 281 patients. CAC and AoC were detected in 81 and 85%, with geometric means (SD) of 52.2 (4.9) and 99.3 (8.2) mg, respectively. By multiple linear regression, independent predictors of both types of calcifications included older age, longer time on dialysis, a history of CVE, of multiple transplantations and of smoking. Other determinants of CAC were male gender, current statin use and history of parathyroidectomy, and other determinants of AoC included higher pulse pressure, shorter time under mycophenolate mofetil and current use of anti-vitamin-K. Conclusion: The prevalence of both CAC and AoC is substantial in RTR. We delineate independent determinants either common to both CAC and AoC or specific to one, and known as classic or chronic kidney disease related risk factors.

The identification of current smokers among renal transplant recipients should start with questioning about lifetime history of smoking and if positive, measurement of cotinine serum level. Indeed up to 34% of current smokers do not acknowledge they are active smokers and would otherwise not offer to participate in programmes to stop smoking.