NDT Advance Access originally published online on March 27, 2009
Nephrology Dialysis Transplantation 2009 24(8):2488-2496; doi:10.1093/ndt/gfp137
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Arterial calcification in patients with chronic kidney disease
1 Department of Internal Medicine 2 Department of Pathology, University of Heidelberg, Heidelberg, Germany 3 Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Poland 4 Institute of Mineralogy, University of Heidelberg, Heidelberg, Germany
Correspondence and offprint requests to: Nadezda Koleganova; E-mail: nad_ko{at}gmx.de
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Abstract |
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Objective. In patients with chronic kidney disease (CKD), aortic calcification is more frequent and severe and it is also predictive of adverse cardiovascular outcome. The aim of the present study was to characterize aortic calcification in renal compared with non-renal patients.
Methods. Aortas of 31 patients with advanced CKD and of 31 age-and gender-matched controls were obtained at autopsy. Calcium and phosphorus content in the aorta was quantitated using x-ray analysis. The expression of calcification-promoting and calcification-inhibiting proteins was assessed using immunohistochemistry.
Results. The calcium and phosphorus content of the aorta was higher in CKD patients than in controls. Even in non-calcified aortic specimens of CKD, staining for Msx-2, BMP-2, bone sialo-protein, TNF-
and nitrotyrosine was significantly more marked compared to controls. The same proteins were immunodetected in calcified aortic specimens of both CKD and controls. In contrast, staining for transglutaminase-2 and Fetuin A was significantly reduced in CKD. Higher expression of cbfa-1 and Pit-1 was observed in all calcified aortas with no difference between CKD and controls. The expression of TNF-, phospho-p38 and Msx-2 was correlated to the intensity of upregulation of BMP-2 and osteoblastic transdifferentiation by VSMC even in non-calcified areas of the aortas of CKD.
Conclusion. The expression of markers characteristic for calcification is not different in calcified aorta of CKD patients compared to controls, but in CKD patients, evidence of inflammation, transformation to an osteoblastic phenotype and reduced expression of transglutaminase are also found even in non-calcified aorta.
Keywords: arterial calcification; cbfa-1; chronic kidney disease; osteoblastic transdifferentiation; TNF-
* These authors contributed equally to this work.
Received for publication: 16.11.08
Accepted in revised form: 9. 3.09