Kerstin Benz1, Ildiko Varga2, Daniel Neureiter3, Valentina Campean2, Christoph Daniel2, Christian Heim4, Albrecht Reimann4, Michael Weyand4, Karl F Hilgers5, Kerstin Amann6. 1. Department of Nephropathology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Erlangen, Germany; Department of Pediatrics, FAU Erlangen-Nürnberg, Erlangen, Germany. 2. Department of Nephropathology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Erlangen, Germany. 3. Department of Pathology, Salzburger Landeskliniken, Salzburg, Austria. 4. Department of Cardiac Surgery, FAU Erlangen-Nürnberg, Erlangen, Germany. 5. Department of Nephrology and Hypertension, FAU Erlangen-Nürnberg, Erlangen, Germany. 6. Department of Nephropathology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Erlangen, Germany. Electronic address: kerstin.amann@uk-erlangen.de.
Abstract
BACKGROUND: While patients with chronic kidney disease (CKD) have a high prevalence of classical coronary risk factors, there is increasing evidence that atherosclerosis is different in renal compared to nonrenal patients. Therefore, the present study compares changes in different vessels obtained at cardiac surgery between patients with early and advanced CKD and nonrenal control patients. METHODS AND RESULTS: Fifty patients undergoing cardiac bypass surgery were divided into three groups: (i) 24 control patients with creatinine <1.3mg/dl, (ii) 14 patients with early CKD (creatinine 1.3-2.0mg/dl), and (iii) 12 patients with advanced CKD (creatinine >2.0mg/dl). Aorta, arteria mammaria interna, and vena saphena (V. saphena) were analyzed using morphometry, Kossa stain for vascular calcification, and immunohistochemistry for markers of inflammation and proosteogenic differentiation of vascular smooth muscle cells (VSMCs). Thereby, aortic wall thickness and calcification score of aortic intima and of V. saphena were significantly higher in advanced CKD patients than in nonrenal control patients, whereas significant vascular inflammation and proosteogenic dedifferentiation of VSMC and calcification of the aortic media were already present in early CKD. Interestingly, marked calcification of the V. saphena magna was seen in advanced CKD. Of note, calcium-phosphate product correlated well with markers of inflammation, but not with calcification itself. CONCLUSIONS: Early stages of CKD are already associated with local up-regulation of proinflammatory and proosteogenic molecules in the vascular wall and calcification of the aortic media. These findings point to the importance of local microinflammation in CKD and may shed new light on the potentially overestimated role of the calcium-phosphate product for vessel calcification.
BACKGROUND: While patients with chronic kidney disease (CKD) have a high prevalence of classical coronary risk factors, there is increasing evidence that atherosclerosis is different in renal compared to nonrenal patients. Therefore, the present study compares changes in different vessels obtained at cardiac surgery between patients with early and advanced CKD and nonrenal control patients. METHODS AND RESULTS: Fifty patients undergoing cardiac bypass surgery were divided into three groups: (i) 24 control patients with creatinine <1.3mg/dl, (ii) 14 patients with early CKD (creatinine 1.3-2.0mg/dl), and (iii) 12 patients with advanced CKD (creatinine >2.0mg/dl). Aorta, arteria mammaria interna, and vena saphena (V. saphena) were analyzed using morphometry, Kossa stain for vascular calcification, and immunohistochemistry for markers of inflammation and proosteogenic differentiation of vascular smooth muscle cells (VSMCs). Thereby, aortic wall thickness and calcification score of aortic intima and of V. saphena were significantly higher in advanced CKD patients than in nonrenal control patients, whereas significant vascular inflammation and proosteogenic dedifferentiation of VSMC and calcification of the aortic media were already present in early CKD. Interestingly, marked calcification of the V. saphena magna was seen in advanced CKD. Of note, calcium-phosphate product correlated well with markers of inflammation, but not with calcification itself. CONCLUSIONS: Early stages of CKD are already associated with local up-regulation of proinflammatory and proosteogenic molecules in the vascular wall and calcification of the aortic media. These findings point to the importance of local microinflammation in CKD and may shed new light on the potentially overestimated role of the calcium-phosphate product for vessel calcification.
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