Aims: Compared to the general population, mortality is significantly increased in renal transplant recipients. In the general population, coronary artery calcification (CAC) and its evolution over time are associated with cardiovascular and all-cause mortality, and the study of this biomarker could provide useful information for describing the long-term progression of coronary heart disease in renal transplant recipients. Methods: We followed up a cohort of 113 renal transplant patients by performing three multi-detector computed tomography studies over 83.6 ± 6.8 months. Data analysis was performed by logistic regression analysis and by mixed linear modelling. Results: Progression was observed in 34.5% of patients. Baseline CAC and time-to-transplantation were the sole variables that predicted CAC evolution over time. Neither classical nor nontraditional risk factors, biomarkers of renal function (GFR) and kidney damage (albuminuria) or biomarkers of bone mineral disorder (BMD), such as serum phosphorus, calcium, and PTH, were associated with the long-term progression of coronary calcification. Serum triglycerides predicted CAC progression only in logistic regression analysis, while in addition to baseline CAC, time to transplantation was the sole variable predicting CAC progression when the data were analyzed by mixed linear modelling. These data suggested that, in addition to the background calcification burden, other unmeasured factors play major roles in promoting the evolution of coronary calcification in the transplant population. Conclusion: CAC progression continued over the long-term follow-up of renal transplant patients. This phenomenon was unaccounted for by classical and nontraditional risk factors, as well as by biomarkers of renal dysfunction and renal damage.

1.
Rabbat CG, Thorpe KE, Russell JD, et al: Comparison of mortality risk for dialysis patients and cadaveric first renal transplant recipients in Ontario, Canada. J Am Soc Nephrol 2000;11:917-922.
2.
United States Renal Data System, 2014 Annual Data Report: Epidemiology of Kidney Disease in the United States. Bethesda, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2014.
3.
Ojo AO, Morales JM, González-Molina M, et al: Comparison of the long-term outcomes of kidney transplantation: USA versus Spain. Nephrol Dial Transplant 2013;28:213-220.
4.
Kahwaji J, Bunnapradist S, Hsu JW, Idroos ML, Dudek R: Cause of death with graft renal function among renal transplant recipients in an integrated healthcare system. Transplantation 2011;91:225-230.
5.
Kondos GT, Hoff JA, Sevrukov A, et al: Electron-beam tomography coronary artery calcium and cardiac events: a 37-month follow-up of 5,635 initially asymptomatic low- to intermediate-risk adults. Circulation 2003;107:2571-2576.
6.
Budoff MJ, Shaw LJ, Liu ST, Weinstein SR, et al: Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol 2007;49:1860-1870.
7.
Arad Y, Goodman KJ, Roth M, et al: Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study. J Am Coll Cardiol 2005;46:158-165.
8.
Budoff MJ, Hokanson JE, Nasir K, et al: Progression of coronary artery calcium predicts all-cause mortality. JACC Cardiovasc Imaging 2010;3:1229-1236.
9.
Seyahi N, Kahveci A, Cebi D, et al: Coronary artery calcification and coronary ischemia in renal transplant recipients. Nephrol Dial Transplant 2011;26:720-726.
10.
Seyahi N, Cebi D, Altiparmak MR, et al: Progression of coronary artery calcification in renal transplant recipients. Nephrol Dial Transplant 2012;27:2101-2107.
11.
McEvoy JW, Blaha MJ, Defilippis AP, et al: Coronary artery calcium progression: an important clinical measurement? A review of published reports. J Am Coll Cardiol 2010;56:1613-1622.
12.
Hokanson JE, MacKenzie T, Kinney G, et al: Evaluating changes in coronary artery calcium: an analytic method that accounts for interscan variability. Am J Roentgenol 2004;182:1327-1332.
13.
Sevrukov AB, Bland JM, Kondos GT: Serial electron beam CT measurements of coronary artery calcium: has your patient's calcium score actually changed? Am J Roentgenol 2005;185:1546-1553.
14.
Reilly MP, Wolfe ML, Localio AR, et al: Coronary artery calcification and cardiovascular risk factors: impact of the analytic approach. Atherosclerosis 2004;173:69-78.
15.
Leffondre K, Boucquemont J, Tripepi G, et al: Analysis of risk factors associated with renal function trajectory over time: a comparison of different statistical approaches. Nephrol Dial Transplant 2015;30:1237-1243.
16.
Gelman A, Hill J: Data Analysis Using Regression and Multilevel/Hierarchical Models. Cambridge, Cambridge University Press, 2007.
17.
Min JK, Lin FY, Gidseg DS, et al: Determinants of coronary calcium conversion among patients with a normal coronary calcium scan: what is the “warranty period” for remaining normal? J Am Coll Cardiol 2010;55:1110-1117.
18.
Gopal A, Nasir K, Liu ST, et al: Coronary calcium progression rates with a zero initial score by electron beam tomography. Int J Cardiol 2007;117:227-231.
19.
Kronmal RA, McClelland RL, Detrano R, et al: Risk factors for the progression of coronary artery calcification in asymptomatic subjects: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation 2007;115:2722-2730.
20.
Grundy SM, Brewer HB Jr, Cleeman JI, et al: Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004;109:433-438.
21.
Postorino M, Marino C, Tripepi G, et al: Abdominal obesity modifies the risk of hypertriglyceridemia for all-cause and cardiovascular mortality in hemodialysis patients. Kidney Int 2011;79:765-772.
22.
Schankel K, Robinson J, Bloom RD, et al: Determinants of coronary artery calcification progression in renal transplant recipients. Am J Transplant 2007;7:2158-2164.
23.
Mazzaferro S, Pasquali M, Taggi F, et al: Progression of coronary artery calcification in renal transplantation and the role of secondary hyperparathyroidism and inflammation. Clin J Am Soc Nephrol 2009;4:685-690.
24.
Bargnoux AS, Dupuy AM, Garrigue V, et al: Evolution of coronary artery calcifications following kidney transplantation: relationship with osteoprotegerin levels. Am J Transplant 2009;9:2571-2579.
25.
Verbeke G, Lesaffre E: A linear mixed-effects model with heterogeneity in the random-effects population. J Am Stat Assoc 1996;91:217-221.
26.
Kasiske BL, Chakkera HA, Roel J, et al: Explained and unexplained ischaemic heart disease risk after renal transplantation. J Am Soc Nephrol 2000;11:1735-1743.
27.
Benedetto FA, Tripepi G, Mallamaci F, et al: Rate of atherosclerotic plaque formation predicts cardiovascular events in ESRD. J Am Soc Nephrol 2008;19:757-763.
28.
Yilmaz MI, Sonmez A, Saglam M, et al: A longitudinal study of inflammation, CKD-mineral bone disorder, and carotid atherosclerosis after renal transplantation. Clin J Am Soc Nephrol 2015;10:471-479.
29.
Hruska KA, Mathew S, Lund RJ, et al: The pathogenesis of vascular calcification in the chronic kidney disease mineral bone disorder: the links between bone and the vasculature. Semin Nephrol 2009;29:156-165.
30.
Baia LC, Humalda JK, Vervloet MG, et al: Fibroblast growth factor 23 and cardiovascular mortality after kidney transplantation. Clin J Am Soc Nephrol 2013;8:1968-1978.
31.
Xiao Y, Peng C, Huang W, et al: Circulating fibroblast growth factor 23 is associated with angiographic severity and extent of coronary artery disease. PLoS One 2013;8:e72545.
32.
Freedman BI, Divers J, Russell GB, et al: Plasma FGF23 and calcified atherosclerotic plaque in African Americans with type 2 diabetes mellitus. Am J Nephrol 2015;42:391-401.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.