Seminars in Nephrology
Volume 29, Issue 2 , Pages 156-165, March 2009

The Pathogenesis of Vascular Calcification in the Chronic Kidney Disease Mineral Bone Disorder: The Links Between Bone and the Vasculature

  • Keith A. Hruska, MD

      Affiliations

    • Department of Pediatrics, Division of Nephrology, Washington University School of Medicine, St. Louis, MO
    • Department of Internal Medicine, Division of Nephrology, Washington University School of Medicine, St. Louis, MO
    • Corresponding Author InformationAddress reprint requests to Keith A. Hruska, MD, Department of Pediatrics, Washington University School of Medicine, Campus Box 8208, 5th Floor MPRB, 660 S. Euclid Ave, St. Louis, MO 63110
  • ,
  • Suresh Mathew, MD

      Affiliations

    • Department of Pediatrics, Division of Nephrology, Washington University School of Medicine, St. Louis, MO
  • ,
  • Richard J. Lund, MD

      Affiliations

    • Renal Division, Department of Medicine, Creighton University, Omaha, NE
  • ,
  • Imran Memon, MD

      Affiliations

    • Department of Pediatrics, Division of Nephrology, Washington University School of Medicine, St. Louis, MO
  • ,
  • Georges Saab, MD

      Affiliations

    • Department of Internal Medicine, Division of Nephrology, Washington University School of Medicine, St. Louis, MO

Summary 

Considerable scientific progress in the pathogenesis of vascular calcification that has accrued in recent years is reviewed in this article. Factors regulating mesenchymal cell differentiation and their role in the neointimal calcification of atherosclerosis and the vascular media calcification observed in chronic kidney disease and diabetes are discussed, as is the role of bone regulatory proteins in bone mineralization and vascular calcification. This includes recent studies related to fetuin-A, and the discovery of a new circulating hormone involved in regulating phosphate homeostasis and sensing skeletal hydroxyapatite precipitation. Finally, the relationship between skeletal mineralization and vascular mineralization is discussed in terms of their links, especially through serum phosphate concentrations.

Keywords: Vascular calcifications, matrix Gla protein, fetuin-A, phosphorus, cardiovascular disease, vitamin D, vascular smooth muscle

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 Supported by National Institutes of Health grants (DK070790, AR41677, and T32-DK062705 to K.A.H.), and by research support from Shire, Wayne, PA; Genzyme, Cambridge, MA; Abbott, Abbott Park, IL; and Fresenius, Waltham, MA.

PII: S0270-9295(09)00009-6

doi:10.1016/j.semnephrol.2009.01.008

Seminars in Nephrology
Volume 29, Issue 2 , Pages 156-165, March 2009