Clinical and Experimental Nephrology

, Volume 9, Issue 4, pp 265–270 | Cite as

Pathogenesis of vascular calcification in dialysis patients

  • Markus Ketteler
  • Ralf Westenfeld
  • Georg Schlieper
  • Vincent Brandenburg


Soft-tissue and vascular calcification are highly prevalent in end-stage renal disease (ESRD). Vascular calcifications manifest as both medial and intimal calcification of arteries and are a hallmark of the accelerated atherosclerosis observed in uremia. The nature of vascular calcification is progressive, and is associated with arterial stiffness and increased cardiovascular mortality. Age, duration of dialysis, and diabetes mellitus are clear determinants of the severity of vascular calcification; however, more recently novel insights into the pathomechanisms of unwanted calcification processes have been gained. Disturbances of mineral metabolism such as hyperphosphatemia and hypercalcemia appear to contribute to progressive calcification, not only by passive precipitation but by actively inducing changes in vascular smooth muscle cell behavior toward an osteoblast-like phenotype. Specific calcium-regulatory proteins may act locally or systemically as calcification inhibitors. Dysregulations of calcification inhibitors, including fetuin-A, matrix Gla protein, osteoprotegerin, and pyrophosphates may also be pathophysiologically relevant factors in the context of uremic extraosseous calcification. In this context, low serum fetuin-A levels were recently found to be associated with increased mortality in cohorts of dialysis patients. This overview intends to summarize current knowledge of the scientific concepts involved in the pathogenesis of extraosseous calcification in ESRD.

Key words

Fetuin-A Matrix Gla protein Osteoprotegerin Pyrophosphates Vascular calcification 


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Copyright information

© Japanese Society of Nephrology 2005

Authors and Affiliations

  • Markus Ketteler
    • 1
  • Ralf Westenfeld
    • 1
  • Georg Schlieper
    • 1
  • Vincent Brandenburg
    • 1
  1. 1.Department of Nephrology and Clinical ImmunologyUniversity Hospital AachenAachenGermany

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