NDT Advance Access originally published online on October 31, 2007
Nephrology Dialysis Transplantation 2008 23(1):82-90; doi:10.1093/ndt/gfm699
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Effect of oral calcium carbonate on aortic calcification in apolipoprotein E-deficient (apoE–/–) mice with chronic renal failure
1Inserm, Unit 845, Necker Hospital, Université Paris V, Paris, France, 2Laboratory of Biochemistry A, Necker Hospital, Université Paris V, Paris, France, 3Inserm, ERI-12, University of Picardie and Amiens University Hospital, Amiens, France, 4Department of Nephrology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland and 5Department of Urology, University Clinical Centre, Medical Faculty, Skopje, Republic of Macedonia
Correspondence and offprint requests to: Prof. Ziad A. Massy, MD, PhD, Inserm ERI-12, Divisions of Clinical Pharmacology and Nephrology, University of Picardie and Amiens University Hospital, Av. Rene Laennec, F-80054 Amiens, France. Tel: + 33 3 2245 5788; Fax: + 33 3 2245 5660; E-mail: massy{at}u-picardie.fr
 |
Abstract |
|---|
Background. In chronic kidney disease (CKD) patients, the intake of calcium-based phosphate binders is associated with a marked progression of coronary artery and aortic calcification, in contrast to patients receiving calcium-free phosphate binders. The aim of this study was to reexamine the role of calcium carbonate in vascular calcification and to analyse its effect on aortic calcification-related gene expression in chronic renal failure (CRF).
Methods. Mice deficient in apolipoprotein E underwent either sham operation or subtotal nephrectomy to create CRF. They were then randomly assigned to one of the three following groups: a control non-CRF group and a CRF group fed on standard diet, and a CRF group fed on calcium carbonate enriched diet, for a period of 8 weeks. Aortic atherosclerotic plaque and calcification were evaluated using quantitative morphologic image processing. Aortic gene and protein expression was examined using immunohistochemistry and Q-PCR methods.
Results. Calcium carbonate supplementation was effective in decreasing serum phosphorus but was associated with a higher serum calcium concentration. Compared with standard diet, calcium carbonate enriched diet unexpectedly induced a significant decrease of both plaque (p < 0.05) and non-plaque-associated calcification surface (p < 0.05) in CRF mice. It also increased osteopontin (OPN) protein expression in atherosclerotic lesion areas of aortic root. There was also a numerical increase in OPN and osteoprotegerin gene expression in total thoracic aorta but the difference did not reach the level of significance. Finally, calcium carbonate did not change the severity of atherosclerotic lesions.
Conclusion. In this experimental model of CRF, calcium carbonate supplementation did not accelerate but instead decreased vascular calcification. If our observation can be extrapolated to humans, it appears to question the contention that calcium carbonate supplementation, at least when given in moderate amounts, necessarily enhances vascular calcification. It is also compatible with the hypothesis of a preponderant role of phosphorus over that of calcium in promoting vascular calcification in CRF.
Keywords: atherosclerosis; calcification; calcium carbonate; CKD; phosphate; uraemia
*Dr. Oliver Phan and Dr Ognen Ivanovski contributed equally to this work.
Received for publication: 12. 7.06
Accepted in revised form: 10. 9.07
CiteULike 
Connotea 
Del.icio.us What's this?
Related articles in NDT:
- After several years of witchhunting, can calcium-based phosphate binding be released on probation?
- Markus Ketteler and Patrick Biggar
NDT 2008 23: 17-19.[Extract] [FREE Full Text] - In this issue ...
NDT 2008 23: i.[Extract] [FREE Full Text]