Arterial Calcification in Chronic Kidney Disease: Key Roles for Calcium and Phosphate

DOI Web Site 35 Citations
  • Catherine M. Shanahan
    From the British Heart Foundation Centre of Excellence (C.M.S., A.K.), Cardiovascular Division, King's College London, London UK; Bioengineering Department (M.H.C., C.M.G.), University of Washington, Seattle, WA.
  • Matthew H. Crouthamel
    From the British Heart Foundation Centre of Excellence (C.M.S., A.K.), Cardiovascular Division, King's College London, London UK; Bioengineering Department (M.H.C., C.M.G.), University of Washington, Seattle, WA.
  • Alexander Kapustin
    From the British Heart Foundation Centre of Excellence (C.M.S., A.K.), Cardiovascular Division, King's College London, London UK; Bioengineering Department (M.H.C., C.M.G.), University of Washington, Seattle, WA.
  • Cecilia M. Giachelli
    From the British Heart Foundation Centre of Excellence (C.M.S., A.K.), Cardiovascular Division, King's College London, London UK; Bioengineering Department (M.H.C., C.M.G.), University of Washington, Seattle, WA.
  • Dwight A. Towler
    editor

Abstract

<jats:p>Vascular calcification contributes to the high risk of cardiovascular mortality in chronic kidney disease (CKD) patients. Dysregulation of calcium (Ca) and phosphate (P) metabolism is common in CKD patients and drives vascular calcification. In this article, we review the physiological regulatory mechanisms for Ca and P homeostasis and the basis for their dysregulation in CKD. In addition, we highlight recent findings indicating that elevated Ca and P have direct effects on vascular smooth muscle cells (VSMCs) that promote vascular calcification, including stimulation of osteogenic/chondrogenic differentiation, vesicle release, apoptosis, loss of inhibitors, and extracellular matrix degradation. These studies suggest a major role for elevated P in promoting osteogenic/chondrogenic differentiation of VSMC, whereas elevated Ca has a predominant role in promoting VSMC apoptosis and vesicle release. Furthermore, the effects of elevated Ca and P are synergistic, providing a major stimulus for vascular calcification in CKD. Unraveling the complex regulatory pathways that mediate the effects of both Ca and P on VSMCs will ultimately provide novel targets and therapies to limit the destructive effects of vascular calcification in CKD patients.</jats:p>

Journal

  • Circulation Research

    Circulation Research 109 (6), 697-711, 2011-09-02

    Ovid Technologies (Wolters Kluwer Health)

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