Role of vascular calcification inhibitors in preventing vascular dysfunction and mortality in hemodialysis patients

Abstract

Cardiovascular events make up the primary cause of death in hemodialysis patients, and the risk for cardiovascular mortality is significantly increased by vascular calcification, a condition observed frequently in this patient population. The mechanisms underlying the pathogenesis of vascular calcification are complex, and many factors facilitate or hinder the development of calcification. In this review, we first summarize the main factors contributing to the pathogenesis of vascular calcification in patients with end-stage renal disease. We then explore the role of calcification inhibitors in the calcification process, as well as their effect on vascular dysfunction and mortality in hemodialysis patients. | INTRODUCTIONThe prevalence of cardiovascular diseases is high among patients with chronic kidney disease (CKD), 1 which increases morbidity and mortality in this population and represents a significant financial burden for both the patients and the healthcare systems. where it may occur in the intima and media layers of the blood vessels and in the cardiac valves. 12 The prevalence of coronary artery calcification is high among dialysis patients; specifically, some degree of coronary artery calcification is observed in 54%-100% of patients, well above the prevalence in the general population. 13Older age, male sex, long duration of dialysis, diabetes, hypertension, smoking, alcohol consumption, hyperphosphatemia, hypercalcemia,

The interplay between mineral metabolism, vascular calcification and inflammation in Chronic Kidney Disease (CKD): challenging old concepts with new facts

“…While many studies have demonstrated the cell toxicity of CaP crystals, it became very clear that highly complex mechanisms exist to control the formation, maturation and pathogenicity of these mineral nucleation sites. This is in line with the currently accepted notion that VC is an active, naturally occurring, and tightly regulated multifactorial process, that must be actively inhibited (extensively reviewed elsewhere [16,86,87]). In fact, CaP nanocrystals are constituents of calciprotein particles (CPPs), mineralization-competent extracellular vesicles (EVs), and mineralized material deposited in the ECM of blood vessels.…”

Update on Chronic Kidney Disease Mineral and Bone Disorder in Cardiovascular Disease

“…These effects can be exacerbated by insufficient activity of calcification inhibitors, including magnesium, vitamin K, or reduced klotho expression. 67,68 For instance, phosphorus loading and klotho depletion consistently induce calcification and reduce vascular compliance in vitro and in vivo in animals. 69–71 Similarly, restoration of normal klotho expression in animals with vitamin D agonists, or reduction in phosphorus exposure through diet can reverse or prevent the calcific phenotype.…”

Effects of Enoxaparin on Intravascular Sclerostin Release in Healthy Men

“…2 –4 Vascular calcification is particularly prevalent and severe in patients with type 2 diabetes mellitus 3,5 and in those with advanced chronic kidney disease. 6,7 Sclerostin is expressed in calcifying vasculature during the highly regulated process of vascular smooth muscle cell (VSMC) reprogramming and differentiation to mineralizing osteoblast-like cells. 2 –4,7 Thus, Scl may be regarded as part of a local counterregulatory mechanism to suppress vascular calcification.…”

“…6,7 Sclerostin is expressed in calcifying vasculature during the highly regulated process of vascular smooth muscle cell (VSMC) reprogramming and differentiation to mineralizing osteoblast-like cells. 2 –4,7 Thus, Scl may be regarded as part of a local counterregulatory mechanism to suppress vascular calcification. 2,6 –8…”

“…2 –4,7 Thus, Scl may be regarded as part of a local counterregulatory mechanism to suppress vascular calcification. 2,6 –8…”