Vascular Calcification in Patients with Chronic Kidney Disease: Types, Clinical Impact and Pathogenesis

Abstract

Vascular calcification plays a major role in cardiovascular disease, which is one of the main causes of mortality in chronic kidney disease patients. Vascular calcification is determined by prevalent traditional and uraemia-related (non-traditional) risk factors. It occurs mainly in the arteries, which are classified into three types according to their size and structural characteristics. In addition, vascular calcification has been associated with bone loss and fractures in chronic kidney disease patients and the general population, stressing the fact that both disorders can share pathogenetic pathways. The strategies to control vascular calcification involve several measures, chief among them the control of hyperphosphataemia. Furthermore, it has been recently described that strategies that reduce bone resorption and increase bone mineralization may decrease the risk of vascular calcifications; however, this approach still remains controversial. The mechanisms involved in vascular calcification are complex and not yet fully understood. Phosphorus plays a major role, while other factors related to bone formation have been recently identified.

Receptor activator of nuclear factor κB ligand/osteoprotegerin axis and vascular calcifications in patients with chronic kidney disease

“…A variety of factors including hormones, cytokines and growth factors regulate its expression. Thus, parathormone (PTH), TNF-α, calcium, corticosteroids and several interleukins (IL-6,-11,-17) increase RANKL expression on osteoblasts, whereas transforming growth factor-β (TGF-β) decreases it [3,5] . OPG is a soluble glycoprotein widely expressed in most human tissues including bone (osteoblests, mesenchymal stem cells), immune cells (T and B cells) and vessels (endothelial and VSMCs).…”

“…The presence of vascular calcifications in CKD has been associated with a number of traditional risk factors including older age, hypertension, dyslipidemia and diabetes mellitus which are highly prevalent in this population, as well as uremia-related risk factors including chronic inflammation, oxidative stress and mineral and bone disorders which are currently under investigation. Of note, mineral alterations (hypercalcemia, hyperphosphatemia) and disorders of bone metabolism (both secondary hyperparathyroidism and adynamic bone disease) are mainly associated with the development and progression of medial but not intimal calcifications [3] . It is now well recognized that vascular calcification is not simply a passive physicochemical process of calcium phosphate deposition but a highly regulated active process similar to normal bone modeling.…”

“…Moreover, recent evidence suggests that the phenotypic transdifferentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells is a key pathogenetic event in the osteogenesis of the vascular wall. A variety of regulatory factors and molecular pathways of this process which regulate bone turnover and/or mineralization have been identified [3] . Although their relative importance in different disease states appear still incompletely understood emerging evidence suggest that the receptor activator of nuclear factor κB (RANK)/RANK Ligand (RANKL)/osteoprotegerin (OPG) system that plays essential roles in the regulation of bone metabolism is also involved in extra-osseous bone formation [4] .…”

Can We Tackle with Vascular Calcification and Arterial Stiffness in Patients with Chronic Kidney Disease?

“…The pathogenesis of vasculopathy in CKD involves traditional risk factors of atherosclerosis (older age, hypertension, dyslipidemia, diabetes mellitus), which are highly prevalent in renal patients, but also several non-traditional or uremia-related risk factors (inflammation, oxidative stress, mineral and bone disorders), which are intensively investigated. In addition, vascular calcifications, particularly of the media, are an almost ubiquitous feature of arterial tree in chronic uremia and a major contributor to accelerated arteriosclerosis and increased arterial stiffness observed in CKD patients [3][4][5]. The extent of vascular calcification and the degree of arterial stiffness, closely interrelated, are non-traditional CVD risk factors and independent predictors of CVD mortality, both in general population and CKD patients [6][7][8][9][10].…”

“…The extent of vascular calcification and the degree of arterial stiffness, closely interrelated, are non-traditional CVD risk factors and independent predictors of CVD mortality, both in general population and CKD patients [6][7][8][9][10]. Several studies have shown that mineral-bone disorders and imbalance between promoters and inhibitors of extra-osseous bone formation are associated with vascular calcification and affect significantly the process of arterial stiffening in renal population, potentially leading to adverse clinical outcomes [5,11]. Moreover, it appears that there is an interaction between bone metabolism and vascular health, placing current understanding of vascular pathophysiology on a bone-vascular axis [12].…”