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Vascular calcification and renal bone disorders.

Lu KC, Wu CC, Yen JF, Liu WC - ScientificWorldJournal (2014)

Bottom Line: Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality.These factors have roles in both promoting and inhibiting VC.In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Department of Medicine, Cardinal Tien Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City 23148, Taiwan.

ABSTRACT
At the early stage of chronic kidney disease (CKD), the systemic mineral metabolism and bone composition start to change. This alteration is known as chronic kidney disease-mineral bone disorder (CKD-MBD). It is well known that the bone turnover disorder is the most common complication of CKD-MBD. Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality. Many factors regulate the VC mechanism, which include imbalances in serum calcium and phosphate, systemic inflammation, RANK/RANKL/OPG triad, aldosterone, microRNAs, osteogenic transdifferentiation, and effects of vitamins. These factors have roles in both promoting and inhibiting VC. Patients with CKD usually have bone turnover problems. Patients with high bone turnover have increase of calcium and phosphate release from the bone. By contrast, when bone turnover is low, serum calcium and phosphate levels are frequently maintained at high levels because the reservoir functions of bone decrease. Both of these conditions will increase the possibility of VC. In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC. However, all of them may fight back the inhibition of bone formation resulting in fragile bone. There are several ways to treat VC depending on the bone turnover status of the individual. The main goals of therapy are to maintain normal bone turnover and protect against VC.

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Related in: MedlinePlus

Scheme for possible mechanisms of vascular calcification in CKD. Vascular calcification is a prominent feature of arterial disease in CKD and may have an impact on cardiovascular mortality through modulating both arteriosclerosis (arterial stiffening) and atherosclerosis. In CKD, abnormal mineral metabolism, predominantly hyperphosphatemia and hypercalcemia, facilitates the progression of the active process of osteogenesis in vascular smooth muscle cells (VSMCs) resulting in arteriosclerosis calcification. However, the disruption of endothelial-derived relaxing factors may signal an early stage in atherosclerosis. Hyperlipidemia, hypertension, metabolic syndrome, and CKD are the major causes of endothelial injury, partly through increase of inflammation or oxidative stress. Major cell players are endothelial cells (or valve interstitial cells; VICs), leukocytes, and intimal smooth muscle cells (SMC). Focal calcification within atherosclerotic plaques is due to both active (osteogenic) and passive (cellular necrosis) processes. The phenotypic osteocyte in calcified vessels/valves may secrete Wnt inhibitors, which may fight back inhibition of bone formation.
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fig1: Scheme for possible mechanisms of vascular calcification in CKD. Vascular calcification is a prominent feature of arterial disease in CKD and may have an impact on cardiovascular mortality through modulating both arteriosclerosis (arterial stiffening) and atherosclerosis. In CKD, abnormal mineral metabolism, predominantly hyperphosphatemia and hypercalcemia, facilitates the progression of the active process of osteogenesis in vascular smooth muscle cells (VSMCs) resulting in arteriosclerosis calcification. However, the disruption of endothelial-derived relaxing factors may signal an early stage in atherosclerosis. Hyperlipidemia, hypertension, metabolic syndrome, and CKD are the major causes of endothelial injury, partly through increase of inflammation or oxidative stress. Major cell players are endothelial cells (or valve interstitial cells; VICs), leukocytes, and intimal smooth muscle cells (SMC). Focal calcification within atherosclerotic plaques is due to both active (osteogenic) and passive (cellular necrosis) processes. The phenotypic osteocyte in calcified vessels/valves may secrete Wnt inhibitors, which may fight back inhibition of bone formation.

Mentions: Twenty years ago, a meaningful inverse association between bone mineral density and aortic calcification was suggested [13]. Some reports have pointed to a perplexing connection between VC and impaired bone metabolism and increased mortality [13–17]. Moreover, severe VCs are likely to be related to an increased frequency of nontraumatic fractures in both the general population and dialysis patients [17]. Usually, osteoporosis and VC are considered to be disorders of aging. However, a new study suggests that besides aging, there are other biological factors influencing the connection between VC and impaired bone metabolism, which contribute to arteriosclerosis and osteoporosis [18]. This review discusses both the pathophysiology of VC and its relationship to impaired bone metabolism in CKD patients (Figure 1).


Vascular calcification and renal bone disorders.

Lu KC, Wu CC, Yen JF, Liu WC - ScientificWorldJournal (2014)

Scheme for possible mechanisms of vascular calcification in CKD. Vascular calcification is a prominent feature of arterial disease in CKD and may have an impact on cardiovascular mortality through modulating both arteriosclerosis (arterial stiffening) and atherosclerosis. In CKD, abnormal mineral metabolism, predominantly hyperphosphatemia and hypercalcemia, facilitates the progression of the active process of osteogenesis in vascular smooth muscle cells (VSMCs) resulting in arteriosclerosis calcification. However, the disruption of endothelial-derived relaxing factors may signal an early stage in atherosclerosis. Hyperlipidemia, hypertension, metabolic syndrome, and CKD are the major causes of endothelial injury, partly through increase of inflammation or oxidative stress. Major cell players are endothelial cells (or valve interstitial cells; VICs), leukocytes, and intimal smooth muscle cells (SMC). Focal calcification within atherosclerotic plaques is due to both active (osteogenic) and passive (cellular necrosis) processes. The phenotypic osteocyte in calcified vessels/valves may secrete Wnt inhibitors, which may fight back inhibition of bone formation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4127293&req=5

fig1: Scheme for possible mechanisms of vascular calcification in CKD. Vascular calcification is a prominent feature of arterial disease in CKD and may have an impact on cardiovascular mortality through modulating both arteriosclerosis (arterial stiffening) and atherosclerosis. In CKD, abnormal mineral metabolism, predominantly hyperphosphatemia and hypercalcemia, facilitates the progression of the active process of osteogenesis in vascular smooth muscle cells (VSMCs) resulting in arteriosclerosis calcification. However, the disruption of endothelial-derived relaxing factors may signal an early stage in atherosclerosis. Hyperlipidemia, hypertension, metabolic syndrome, and CKD are the major causes of endothelial injury, partly through increase of inflammation or oxidative stress. Major cell players are endothelial cells (or valve interstitial cells; VICs), leukocytes, and intimal smooth muscle cells (SMC). Focal calcification within atherosclerotic plaques is due to both active (osteogenic) and passive (cellular necrosis) processes. The phenotypic osteocyte in calcified vessels/valves may secrete Wnt inhibitors, which may fight back inhibition of bone formation.
Mentions: Twenty years ago, a meaningful inverse association between bone mineral density and aortic calcification was suggested [13]. Some reports have pointed to a perplexing connection between VC and impaired bone metabolism and increased mortality [13–17]. Moreover, severe VCs are likely to be related to an increased frequency of nontraumatic fractures in both the general population and dialysis patients [17]. Usually, osteoporosis and VC are considered to be disorders of aging. However, a new study suggests that besides aging, there are other biological factors influencing the connection between VC and impaired bone metabolism, which contribute to arteriosclerosis and osteoporosis [18]. This review discusses both the pathophysiology of VC and its relationship to impaired bone metabolism in CKD patients (Figure 1).

Bottom Line: Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality.These factors have roles in both promoting and inhibiting VC.In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Department of Medicine, Cardinal Tien Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City 23148, Taiwan.

ABSTRACT
At the early stage of chronic kidney disease (CKD), the systemic mineral metabolism and bone composition start to change. This alteration is known as chronic kidney disease-mineral bone disorder (CKD-MBD). It is well known that the bone turnover disorder is the most common complication of CKD-MBD. Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality. Many factors regulate the VC mechanism, which include imbalances in serum calcium and phosphate, systemic inflammation, RANK/RANKL/OPG triad, aldosterone, microRNAs, osteogenic transdifferentiation, and effects of vitamins. These factors have roles in both promoting and inhibiting VC. Patients with CKD usually have bone turnover problems. Patients with high bone turnover have increase of calcium and phosphate release from the bone. By contrast, when bone turnover is low, serum calcium and phosphate levels are frequently maintained at high levels because the reservoir functions of bone decrease. Both of these conditions will increase the possibility of VC. In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC. However, all of them may fight back the inhibition of bone formation resulting in fragile bone. There are several ways to treat VC depending on the bone turnover status of the individual. The main goals of therapy are to maintain normal bone turnover and protect against VC.

Show MeSH
Related in: MedlinePlus