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Calcification of Coronary Intima and Media: Immunohistochemistry, Backscatter Imaging, and X-Ray Analysis in Renal and Nonrenal Patients

Marie-Luise Gross^*, Hans-Peter Meyer, Heike Ziebart^*, Peter Rieger^*, Uta Wenzel^*, Kerstin Amann, Irina Berger^*, Marcin Adamczak, Peter Schirmacher^*, and Eberhard Ritz^||

Institutes of ^* Pathology and Mineralogy, Heidelberg, Institute of Pathology, Erlangen, and ^|| Department of Internal Medicine, Division Nephrology, Heidelberg, Germany; and Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Poland

Address correspondence to: Dr. Marie-Luise Gross, Institute of Pathology, INF 220/221, 69120 Heidelberg, Germany. Phone: +49-6221-562668; Fax: +49-6221-565251; E-mail: marie-luise_gross{at}med.uni-heidelberg.de

Coronary calcification is a potent predictor of cardiac events. In patients with chronic renal disease, both prevalence and intensity of coronary calcification are increased. It has remained uncertain whether it is the intima of the coronaries or the media that is calcified and whether the morphologic details of calcified plaques differ between renal and nonrenal patients. Autopsy samples of coronaries were obtained from standard sites in 23 renal and 23 age- and gender-matched nonuremic patients. Specimens were examined using light and electron microscopy, immunohistochemistry, backscatter imaging, and x-ray analysis. In coronaries, calcified plaques occupied a similar proportion of the intima area in renal versus nonrenal patients (17.3 ± 11.9 versus 18.1 ± 11.9%) but occupied a significantly higher proportion of the media (16.6 ± 10.6 versus 3.8 ± 2.31%). Expression of the proteins osteocalcin, C-reactive protein, TGF-ß, and collagen IV was significantly more intensive around coronary plaques of renal compared with nonrenal patients. The non–plaque-bearing intima of renal patients showed minimal staining for fetuin, but fetuin staining was seen surrounding calcified plaques. In addition, more pronounced deposition of C5b-9 was found around coronary plaques of renal patients, and glycophorin deposition pointed to more past intraplaque hemorrhage in renal patients. Calcification by electron backscatter analysis is more intense in the coronary media, but not if the intima is more intense in renal compared with nonrenal patients. A more marked inflammatory response in renal patients is suggested by more frequent presence and greater intensity of markers of inflammation.

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