Journal Article

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

Ayinuer Adijiang, Sumie Goto, Satsuki Uramoto, Fuyuhiko Nishijima and Toshimitsu Niwa

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 23, issue 6, pages 1892-1901
Published in print June 2008 | ISSN: 0931-0509
Published online March 2008 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfm861
Indoxyl sulphate promotes aortic calcification with expression of osteoblast-specific proteins in hypertensive rats

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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.

Keywords: aortic calcification; indoxyl sulphate; organic anion transporter; osteopontin; uraemic toxin

Journal Article.  5039 words.  Illustrated.

Subjects: Nephrology

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