Vascular calcification: The killer of patients with chronic kidney disease

Masahide Mizobuchi, Dwight Towler, Eduardo Slatopolsky

Research output: Contribution to journalReview article

284 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1453-1464
Number of pages12
JournalJournal of the American Society of Nephrology
Volume20
Issue number7
DOIs
StatePublished - Jul 1 2009

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Vascular Calcification
Chronic Renal Insufficiency
Kidney Diseases
Oxidative Stress
alpha-2-HS-Glycoprotein
Hyperphosphatemia
Osteopontin
Mortality
Uremia
Dyslipidemias
Osteoblasts
Osteogenesis
Chronic Kidney Failure
Smooth Muscle Myocytes
Blood Vessels
Cause of Death
Transcription Factors
Research Personnel
Inflammation
Bone and Bones

ASJC Scopus subject areas

  • Nephrology

Cite this

Vascular calcification : The killer of patients with chronic kidney disease. / Mizobuchi, Masahide; Towler, Dwight; Slatopolsky, Eduardo.

In: Journal of the American Society of Nephrology, Vol. 20, No. 7, 01.07.2009, p. 1453-1464.

Research output: Contribution to journalReview article

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