Progression of Coronary Artery Calcification and Thoracic Aorta Calcification in Kidney Transplant Recipients

Abstract

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.

A Randomized Study Evaluating Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients With Persistent Hyperparathyroidism

“…The development of novel immunosuppressive therapies has led to a tremendous increase in the 1-year survival rates of renal allografts (1). Accordingly, improving the long-term survival and quality of life for renal transplant recipients has become a major focus of posttransplant patient care and includes prevention of cardiovascular complications (2,3), diabetes mellitus and fractures secondary to bone disease (4,5).…”

Calcification Propensity and Survival among Renal Transplant Recipients

“…Vascular calcification progresses substantially even in stable RTR and is an established predictor of morbidity and mortality. [3][4][5] The so-called traditional risk factors tobacco use, diabetes, obesity, hypertension, and dyslipidemia (i.e., the Framingham risk factors) have been identified as independent predictors of cardiovascular disease after kidney transplantation. 6 Biomineralization is a tightly regulated and location-specific process, determined by both inhibitors and promoters of calcification.…”

Persistence of Vascular Calcification after Reversal of Uremia

“…9 Although renal failure was eliminated, this experimental approach was complicated by the metabolic derangements in transplant patients that can cause progression of atherosclerosis and the accompanying calcification. 11 Treatments to correct altered mineral metabolism in patients with renal failure can slow progression of vascular calcification, but reversal has not been shown. Treatment with etidronate appeared to reduce coronary artery calcification in some, but not all, patients with endstage renal disease.…”

“…However, this calcification is largely atherosclerotic 10 and can progress after transplantation as a result of other metabolic factors. 11 Studies in uremic animals have been limited to an atherosclerotic model in mice in which sevelamer appeared to reverse some calcification. 12 Reversibility of medial calcification has been shown in nonuremic animal models 13e15 and in patients with generalized arterial calcification of infancy.…”