Osteoprotegerin and Progression of Coronary and Aortic Calcifications in Chronic Kidney Disease M. Mesquita, A. Demulder, F. Wolff, C. Mélot, N. Damry, M. Dratwa, and P. Bergmann ABSTRACT Vascular calcifications (VCs) are important predictors of cardiovascular mortality in patients with chronic kidney disease (CKD). We have shown previously that osteopro- tegerin (OPG), a potential early biomarker for VC, was an independent predictor of mortality in CKD patients. The aim of our study was to follow longitudinally coronary and aortic VCs. VCs were measured using Siemens 16 detector CT in a group of predialysis and hemodialyzed patients before and after a follow-up of 4 years. Some of these patients were transplanted in the meantime. Renal function, calcium, phosphate, iPTH, hs-CRP (high sensitive protein C reactive), and OPG serum levels were also compared. VCs progressed in predialysis, hemodialyzed, and transplanted patients but the progression was not the same in all arterial beds. A progression of coronary calcifications was observed in predialysis and transplanted patients, while aortic calcifications worsened significantly only in hemodialyzed patients. OPG serum levels and hs-CRP were significantly lower among transplanted patients. We concluded that VC depends on the severity of the kidney disease. Transplanted patients are not protected from VC, yet their OPG serum levels were significantly lower, suggesting that there is no link between between OPG levels and severity of VC. Longer follow-up of these patients would be necessary to assess whether a decline in OPG correlates with better survival. V ASCULAR CALCIFICATIONS (VCs), an important predictor of all-cause as well as cardiovascular mor- tality, are frequent among patients with chronic kidney disease (CKD). 1 The pathogenesis of VC remains unclear. It has been shown that VC is an active process involving phenotypic transformation of vascular smooth muscle cells into bone-forming osteoblast-like cells. These cells are able to express and/or release bone matrix proteins, including osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), and osteopontin, which are necessary to support the calcification process. Several fac- tors induce or modulate this phenotypic transportation such as transforming growth factor beta 1 (TGF1) and PPAR (peroxisome proliferator- activated receptor ) and tumor necrosis factor (TNF) . 2–4 The etiology and progression of VC in uremic patients is probably multifactorial; dysregulation of mineral me- tabolism in CKD patients could be a main determinant of VC risk, 5 but factors apparently not related to mineral metabolism such as aging, diabetes, inflammation, and body mass index, 6–9 have been suspected to contribute to VC. It has also been shown that the use of calcium-based phosphate binders increased the extent of arterial calci- fications. 10 A variety of imaging methods allow sensitive detection of vascular calcifications. The siemens 16 detector com- puted tomography (MDCT) scores coronary artery (CAC) and aortic arch calcifications (Ao AC). 11–13 Nev- ertheless, it would be of clinical relevance to have biomarkers that predict early calcification as well as progression of calcification in uremic patients. A poten- From the Clinics of Nephrology and Dialysis (M.M., M.D.), CHU Brugmann, Brussels, Belgium; Department of Clinical Bi- ology (A.D., F.W.), CHU Brugmann, Brussels, Belgium; Intensive Care Unit (C.M.), Erasme Academic Hospital, Brussels, Belgium; Department of Radiology (N.D.), CHU Brugmann, Brussels, Belgium; and Laboratory of Experimental Medicine and Depart- ment of Nuclear Medicine (P.B.), CHU Brugmann, Free Univer- sity of Brussels, Brussels, Belgium. Address reprint requests to Mesquita Maria, Clinics of Nephrol- ogy and Dialysis, CHU Brugmann, Place A Van Gehuchten 4, 1020 Bruxelles, Belgium. E-mail: maria.mesquita@chu-brugmann.be 0041-1345/10/$–see front matter © 2010 by Elsevier Inc. All rights reserved. doi:10.1016/j.transproceed.2010.09.129 360 Park Avenue South, New York, NY 10010-1710 3444 Transplantation Proceedings, 42, 3444 –3449 (2010)