Vascular Calcification in Chronic Kidney Disease: The Role of Inflammation

Abstract

Cardiovascular complications are extremely frequent in patients with chronic kidney disease (CKD) and death from cardiac causes is the most common cause of death in this particular population. Cardiovascular disease is approximately 3 times more frequent in patients with CKD than in other known cardiovascular risk groups and cardiovascular mortality is approximately 10-fold more frequent in patients on dialysis compared to the age- and sex-matched segments of the nonrenal population. Among other structural and functional factors advanced calcification of atherosclerotic plaques as well as of the arterial and venous media has been described as potentially relevant for this high cardiovascular morbidity and mortality. One potential explanation for this exceedingly high vascular calcification in animal models as well as in patients with CKD increased systemic and most importantly local (micro)inflammation that has been shown to favor the development of calcifying particles by multiple ways. Of note, local vascular upregulation of proinflammatory and proosteogenic molecules is already present at early stages of CKD and may thus be operative for vascular calcification. In addition, increased expression of costimulatory molecules and mast cells has also been documented in patients with CKD pointing to a more inflammatory and potentially less stable phenotype of coronary atherosclerotic plaques in CKD.

Figure 1

(a-f) Representative vascular findings in nonrenal control patients (a, c, e) and patients with chronic kidney disease (CKD). (a, b) Marked thickening of coronary arteries in CKD patients (b) compared to nonrenal controls (a). HE-stain. (c, d) Marked calcification of the arterial intima and media and atherosclerotic coronary plaques in CKD patients (d) compared to nonrenal controls (d). Von Kossa stain. (e, f) Increased number of CD68 positive macrophages in the vascular wall of CKD patients (f) compared to nonrenal controls (e). Immunohistochemistry.

Figure 2

(a-f) Representative vascular changes in nonrenal control patients (a, c, e) and patients with early chronic kidney disease (CKD). (a, b) Increased expression of galectin-3 in arteria mammaria int. in early CKD patients (b) compared to nonrenal controls (a). Immunohistochemistry. (c, d) Marked increase in STAB2 expression in arteria mammaria int. in early CKD patients (d) compared to nonrenal controls (d). Immunohistochemistry. (e, f) Increased staining for C-reactive protein (CRP) in vena saphena magna in early CKD patients (f) compared to nonrenal controls (e). Immunohistochemistry.