Year: 2013
Type: article
Abstract: The frequency of vascular calcification is significantly increased in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). This complication was reported even in predialysis era and before widespread use of calcium and vitamin D supplements and calciumcontaining phosphate binders. 1,2 Coronary artery calcification has been shown in up to 92% of young ESRD patient with sequential computed tomography and electrocardiography gating. 3 Even conventional radiographic studies have revealed vascular calcification in about 60% of ESRD patients with 57% progression over time. 4 Vascular calcification is histologically divided into 4 main types of atherosclerotic intimal calcification, medial artery calcification (Monckeberg sclerosis), cardiac valve calcification, and arteriole calcification in the form of calciphylaxis. 5 Various risk factors have been associated with the pathogenesis of vascular calcification, including valvular calcification. Generally, the underlying risk factors can be divided into genetic susceptibility, mineral metabolismrelated factors, and mineral metabolism-unrelated factors. 6 Polymorphism in glucose transporter-1 XbaI gene has been linked to the increased risk of vascular calcification in ESRD patients, and a number of murine models susceptible to vascular calcification have been developed, which are null in various genes inhibiting vascular calcification such as apolipoprotein E, low-density lipoprotein-receptor, matrix Gla protein, Klotho, and fetuin-A. Regarding the factors related to mineral metabolism, increased phosphate level and high dose active vitamin D supplement are the mainly suggested promoters of vascular calcification. Also, most authorities believe that parathyroid hormone (PTH) may have a protective effect against vascular calcification, and the severity of vascular calcification may increase in conditions of adynamic bone disease and low PTH. 6 Among factors unrelated to mineral metabolism, derangements in activators of vascular calcification, such as bone morphogenetic protein 2 and receptor activator of nuclear factor-kappa B ligand or inhibitors of vascular calcification such as matrix Gla protein, bone morphogenetic protein 7, osteopontin, osteoprotegerin, fetuin-A, Smad6, and pyrophosphate, may be linked to vascular calcification. Decreased levels of fetuin-A is observed in maintenance hemodialysis patients and has been correlated with higher rates of vascular calcification, cardiovascualr mortality, and malnutrition-inflammation states as assessed by subjective global assessment and high C-reactive protein levels. 7-9 Results of these studies suggest that fetuin-A is both a calcification inhibitor protein and a negative acute-phase reactant and acts as a link between inflammation and atherosclerosis in patients with CKD. Also, circulating matrix Gla protein is decreased in dialysis patients and has been proposed as a predictor of mortality in these patients. Low levels of vitamin K, which is needed for activation of this calcification inhibitor, have been shown in the majority of dialysis patients. Whether vitamin K supplementation improves outcome in these patients is pending to further studies. 10 Cardiac valve calcification has been reported in up to 47% of hemodialysis patients with increased risk of mortality compared to those without valvular calcification. 11-13 The mechanisms responsible for the increased cardiovascular mortality and morbidity in valvular calcifications are not well understood. Mitral annulus calcification has been associated with higher frequency of rhythm and cardiac conduction defects. 14 However, aortic valve calcification may represent a surrogate marker either for underlying atherosclerotic disease or
Author: Shahrzad Ossareh
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W2118916564