Indoxyl sulphate promotes aortic calcification with expression of osteoblast-specific proteins in hypertensive rats

Nephrol Dial Transplant. 2008 Jun;23(6):1892-901. doi: 10.1093/ndt/gfm861. Epub 2008 Mar 11.


Background: Stage 5 chronic kidney disease (CKD) is associated with enhanced aortic calcification. The aim of this study was to determine if the administration of indoxyl sulphate (IS), a uraemic toxin, stimulates the progression of aortic calcification.

Methods: The rat groups consisted of (i) Dahl salt-resistant normotensive rats (DR) with intake of 0.3% salt, (ii) Dahl salt-sensitive hypertensive rats (DS) with intake of 2.0% salt and (iii) Dahl salt-sensitive hypertensive IS-administered rats (DS-IS) with intake of 2.0% salt and 200 mg/kg of IS in water. After 30 weeks, their aortic and kidney tissues were excised for histological and immunohistochemical analyses.

Results: Severe vascular calcification was observed by von Kossa staining in the arcuate aorta of all the DS-IS rats, but hardly in DS or DR rats. Immunohistochemistry demonstrated that osteopontin, core binding factor 1 (Cbfal), alkaline phosphatase (ALP), osteocalcin, IS and organic anion transporter (OAT) 3 were colocalized in the cells embedded in the aortic calcification area of DS-IS rats. Wall thickness was significantly increased in arcuate, thoracic and abdominal aortas of DS-IS rats compared with DS and DR rats. DS-IS rats showed significantly increased extent of glomerular hypertrophy, mesangial expansion, Masson's trichrome-positive tubulointerstitial area and glomerular and tubulointerstitial expression of transforming growth factor-ssl as compared with DS and DR rats.

Conclusions: IS induced aortic calcification with expression of osteoblast-specific proteins and aortic wall thickening. IS is not only a nephrotoxin but also a vascular toxin, and may contribute to the progression of aortic calcification in stage 5 CKD patients.

Publication types

  • Comparative Study

MeSH terms

  • Analysis of Variance
  • Animals
  • Aortic Diseases / chemically induced
  • Aortic Diseases / metabolism*
  • Aortic Diseases / pathology*
  • Blood Pressure / drug effects
  • Calcinosis / chemically induced
  • Calcinosis / metabolism*
  • Calcinosis / pathology*
  • Core Binding Factors / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Immunohistochemistry
  • Indican
  • Kidney Glomerulus / pathology
  • Organic Anion Transporters, Sodium-Independent / metabolism
  • Osteoblasts / metabolism*
  • Osteopontin / metabolism
  • Random Allocation
  • Rats
  • Rats, Inbred Dahl
  • Sodium Chloride, Dietary


  • Core Binding Factors
  • Organic Anion Transporters, Sodium-Independent
  • Slco1a5 protein, rat
  • Sodium Chloride, Dietary
  • Osteopontin
  • Indican