Annales Pharmaceutiques Françaises (2009) 67, 234—240 GENERAL REVIEW Pathophysiological mechanisms and consequences of cardiovascular calcifications: Role of uremic toxicity Mécanismes physiopathologiques et conséquences des calcifications cardiovasculaires : rôle de la toxicité urémique J.-M. Chillon a,b,c , A. Mozar a,b , I. Six a,b , J. Maizel a,b,c , J.-M. Bugnicourt c , S. Kamel a,b,c , M. Slama a,b,c , M. Brazier a,b,c , Z.A. Massy a,b,c,* a Inserm ERI-12, Amiens, France b Faculty of Medicine/Pharmacy, UPJV, Amiens, France c Amiens University Hospital, Amiens, France Received 19 February 2009; accepted 6 April 2009 Available online 23 May 2009 KEYWORDS Chronic kidney disease; Uremic toxicity; Cardiovascular calcification; Osteoclast-like differentiation; Osteoblast-like phenotype Summary Chronic kidney disease (CKD) represents an accelerated model of the active car- diovascular calcification process. Recent data from our laboratory indicate the presence of a possible vascular remodeling leading to vascular calcification similar to that observed in bone tissue, and emphasize the role of uremic toxicity. Uremic serum not only induces differentiation of smooth muscle cells into an osteoblast-like phenotype but also inhibits the differentiation of monocyte-macrophages cells into osteoclasts. The imbalance between the two processes in vascular walls in favor of osteoblast-like formation could lead to calcification. Cardiovascu- lar calcification may contribute to the high rate of cardiovascular disease in patients with CKD. However, uremic toxicity, which participates in the pathogenesis of cardiovascular calcification, seems to have independent effects on vascular walls, at least in the early stages of CKD. We recently reported that functional (i.e. endothelial dysfunction) rather than structural changes, including vascular calcification, may contribute to the aortic hemodynamic changes observed during early CKD. Uremic toxicity also appears to be associated with calcification of intracra- nial arteries. Knowledge concerning the pathogenesis and consequences of cardiovascular * Corresponding author. Division(s) of Clinical Pharmacology and Nephrology, Amiens University Hospital, avenue Réné-Laennec, 80054 Amiens, France E-mail address: massy@u-picardie.fr (Z.A. Massy). 0003-4509/$ — see front matter © 2009 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.pharma.2009.04.001