Phosphate toxicity and vascular mineralization

Contrib Nephrol. 2013:180:74-85. doi: 10.1159/000346784. Epub 2013 May 3.

Abstract

Vascular calcification or mineralization is a major complication seen in patients with advanced stages of chronic kidney disease (CKD), and it is associated with markedly increased morbidity and mortality. Most of the CKD-related vascular mineralization is attributable to abnormal mineral ion metabolism. Elevated serum calcium and phosphate levels, along with increased calcium-phosphorus byproduct, and the use of active vitamin D metabolites are thought to be the predisposing factors for developing vascular mineralization in patients with CKD. Recent experimental studies have shown that vascular mineralization can be suppressed by reducing serum phosphate levels, even in the presence of extremely high serum calcium and 1,25-dihydroxyvitamin D levels, indicating that reducing 'phosphate toxicity' should be the important therapeutic priority in CKD patients for minimizing the risk of developing vascular mineralization and the disease progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Calcinosis / drug therapy
  • Calcinosis / etiology*
  • Calcinosis / metabolism
  • Calcinosis / prevention & control
  • Coronary Disease / etiology
  • Disease Models, Animal
  • Disease Progression
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / physiology
  • Glucuronidase / deficiency
  • Glucuronidase / physiology
  • Humans
  • Hydroxyapatites / metabolism
  • Hypercalcemia / complications
  • Hypercalcemia / metabolism
  • Hypercalcemia / pathology
  • Hyperphosphatemia / complications
  • Hyperphosphatemia / genetics
  • Hyperphosphatemia / metabolism*
  • Hyperphosphatemia / pathology
  • Klotho Proteins
  • Mice
  • Models, Biological
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Phosphates / metabolism*
  • Renal Dialysis
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / metabolism*
  • Renal Insufficiency, Chronic / pathology
  • Renal Insufficiency, Chronic / therapy
  • Vascular Diseases / drug therapy
  • Vascular Diseases / etiology*
  • Vascular Diseases / metabolism
  • Vascular Diseases / prevention & control
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood

Substances

  • Hydroxyapatites
  • Phosphates
  • Vitamin D
  • Fibroblast Growth Factors
  • 1,25-dihydroxyvitamin D
  • Fibroblast Growth Factor-23
  • Glucuronidase
  • Klotho Proteins