2008 JASN IMPACT FACTOR 7.505	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2008070692v1 20/7/1453    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Mizobuchi, M. Articles by Slatopolsky, E. PubMed PubMed Citation Articles by Mizobuchi, M. Articles by Slatopolsky, E.

Vascular Calcification: The Killer of Patients with Chronic Kidney Disease

Masahide Mizobuchi^*, Dwight Towler and Eduardo Slatopolsky^*

^* Renal Division and Center for Cardiovascular Research, Division of Bone and Mineral Diseases, Department of Medicine, Washington University, St. Louis, Missouri

Correspondence: Dr. Eduardo Slatopolsky, Department of Medicine, Renal Division, Box 8126, Washington University School of Medicine, St. Louis, MO 63110. Phone: 314-362-7208; Fax: 314-362-7875; E-mail: eslatopo{at}im.wustl.edu

Cardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). Vascular calcification is a common complication in CKD, and investigators have demonstrated that the extent and histoanatomic type of vascular calcification are predictors of subsequent vascular mortality. Although research efforts in the past decade have greatly improved our knowledge of the multiple factors and mechanisms involved in vascular calcification in patients with kidney disease, many questions remain unanswered. No longer can we accept the concept that vascular calcification in CKD is a passive process resulting from an elevated calcium-phosphate product. Rather, as a result of the metabolic insults of diabetes, dyslipidemia, oxidative stress, uremia, and hyperphosphatemia, "osteoblast-like" cells form in the vessel wall. These mineralizing cells as well as the recruitment of undifferentiated progenitors to the osteochondrocyte lineage play a critical role in the calcification process. Important transcription factors such as Msx 2, osterix, and RUNX2 are crucial in the programming of osteogenesis. Thus, the simultaneous increase in arterial osteochondrocytic programs and reduction in active cellular defense mechanisms creates the "perfect storm" of vascular calcification seen in ESRD. Innovative clinical studies addressing the combined use of inhibitors that work on vascular calcification through distinct molecular mechanisms, such as fetuin-A, osteopontin, and bone morphogenic protein 7, among others, will be necessary to reduce significantly the accrual of vascular calcifications and cardiovascular mortality in kidney disease. In addition, the roles of oxidative stress and inflammation on the fate of smooth muscle vascular cells and their function deserve further translational investigation.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673