Vascular Calcification in Patients With Renal Failure: Culprit or Innocent Bystander? Santo Dellegrottaglie, MD a , Rajiv Saran, MD b , Sanjay Rajagopalan, MD a, * a Zena and Michael A. Wiener Cardiovascular Institute and Marie-Jose ´e and Henry R. Kravis Center for Cardiovascular Health, Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029, USA b Division of Nephrology, University of Michigan, 315 W. Huron, Ann Arbor, MI 48103, USA There is an emerging epidemic of chronic kidney disease (CKD) in developed countries, driven primarily by the aging of the global population and the escalating numbers of patients who have type 2 diabetes mellitus [1]. Recent reports suggest that as many as 6% to 11% of the adult population could have some degree of CKD, and this estimate is supported by the dramatic rise in the number of people with end- stage renal disease (ESRD) [2]. What is not readily appreciated is that the preponderance of patients who have CKD are more likely to die from cardiovascular disease than to go on to ESRD requiring renal replacement therapy [3]. This likelihood is reflected in the increased referrals to cardiologists of patients who have cardiovas- cular disease and coexisting CKD. CKD has clearly emerged as an independent risk factor for cardiovascular events, particularly in higher-risk populations [4–6]. Recently, an indepen- dent and graded association between reduced renal function and risk of cardiovascular events has been demonstrated in a single large cohort of patients (approximately 1 million individuals) [7]. The con- comitance of a higher incidence of traditional cardiovascular risk factors, such as older age, hypertension, dyslipidemia, and diabetes, and risk factors specific to CKD (ie, albuminuria, anemia, abnormal calcium and phosphate metabolism, ex- tracellular fluid volume overload, electrolyte imbal- ance) may partly explain the high prevalence of cardiovascular disease in these patients [8]. A number of other pathophysiologic variables that are driven by the uremic milieu, such as oxidative stress, inflammation, and endothelial dysfunction, may promote the atherosclerotic process. The interaction among this multiplicity of factors has been hypothesized to promote the myocardial and vascular complications commonly encountered in CKD patients. In particular, atherosclerosis is common in patients who have CKD; the lesions typically are associated with marked vascular calcification (VC) [9,10]. The traditional variables of risk are poorly predictive of cardiovascular events in this pop- ulation. With the availability of feasible and reproducible imaging modalities, however, there has been a great interest in surrogate markers of cardiovascular risk in patients who have renal failure. Specifically, in view of the higher pre- dilection for VC in patients who have CKD, it has been hypothesized that determining vessel calcium scores by CT may be a helpful marker of the ex- tension of atherosclerosis and in predicting events in this population. This article briefly summarizes the current knowledge regarding (1) the mechanisms respon- sible for VC and its relationship to the athero- sclerotic process (with a focus on uremic patients) and (2) the detection of VC and its prevalence in patients who have CKD and ESRD. * Corresponding author: Sanjay Rajagopalan, MD Cardiovascular Institute, Mount Sinai Medical Center Box 1030, One Gustave L. Levy Place, New York, NY 10029. E-mail address: sanjay.rajagopalan@mssm.edu (S. Rajagopalan). 0733-8651/05/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ccl.2005.04.001 cardiology.theclinics.com Cardiol Clin 23 (2005) 373–384