Cardiovascular Calcification Heterogeneity in Chronic Kidney Disease

Abstract

Patients with chronic kidney disease (CKD) exhibit tremendously elevated risk for cardiovascular disease, particularly ischemic heart disease, due to premature vascular and cardiac aging and accelerated ectopic calcification. The presence of cardiovascular calcification associates with increased risk in patients with CKD. Disturbed mineral homeostasis and diverse comorbidities in these patients drive increased systemic cardiovascular calcification in different manifestations with diverse clinical consequences, like plaque instability, vessel stiffening, and aortic stenosis. This review outlines the heterogeneity in calcification patterning, including mineral type and location and potential implications on clinical outcomes. The advent of therapeutics currently in clinical trials may reduce CKD-associated morbidity. Development of therapeutics for cardiovascular calcification begins with the premise that less mineral is better. While restoring diseased tissues to a noncalcified homeostasis remains the ultimate goal, in some cases, calcific mineral may play a protective role, such as in atherosclerotic plaques. Therefore, developing treatments for ectopic calcification may require a nuanced approach that considers individual patient risk factors. Here, we discuss the most common cardiac and vascular calcification pathologies observed in CKD, how mineral in these tissues affects function, and the potential outcomes and considerations for therapeutic strategies that seek to disrupt the nucleation and growth of mineral. Finally, we discuss future patient-specific considerations for treating cardiac and vascular calcification in patients with CKD—a population in need of anticalcification therapies.

Intracellular proteomics and extracellular vesiculomics as a metric of disease recapitulation in 3D-bioprinted aortic valve arrays

“…To partially address this phenomenon, we have included two different calcification induction medias in this study-OM and procalcifying media (PM). PM induces calcification through ectopic calcification and mineralization, similar to what is observed in chronic kidney disease (61). OM, however, encourages fibrotic collagen deposition and subsequent osteogenesis via the introduction of ascorbic acid, an essential cofactor for collagen production, secretion, and cross-linking (62).…”

Phosphate in Cardiovascular Disease: From New Insights Into Molecular Mechanisms to Clinical Implications

“…Calcification of these tissues is characteristic of patients with CKD-MBD but also occurs with healthy aging and is accelerated by diabetes. 80,81 In a subgroup of patients from the Multi-Ethnic Study of Atherosclerosis who had moderate CKD and no clinical CVD, higher serum phosphate levels, even within the normal range, were associated with a greater prevalence of vascular and valvular calcification. 82 Further, in the general population, higher levels of serum phosphate within the normal range are associated with increased coronary artery calcification.…”

“…83 While statistics and clinical measurement techniques vary, there is a marked increased risk and, perhaps more importantly, a higher burden of cardiovascular calcification in patients with impaired kidney function. 80…”

“…83 While statistics and clinical measurement techniques vary, there is a marked increased risk and, perhaps more importantly, a higher burden of cardiovascular calcification in patients with impaired kidney function. 80 Cardiovascular calcification is strongly associated with an increased risk of cardiovascular morbidity and mortality in both patients with CKD and the general population. [84][85][86][87] Of note, systemic phosphate dysregulation or hyperphosphatemia is not necessary for the development of valvular and vascular calcification and in many cases occurs as a result of local inorganic phosphate abundance regulated by other factors, such as inflammation.…”

Increased Risk of Cardiovascular Complications in Chronic Kidney Disease: Introduction to a Compendium

“…Therapeutic strategies aiming to improve endothelial health are also covered in this article. Hutcheson and Goettsch 15 provide deeper insights into cardiovascular calcification in CKD, with a focus on its heterogeneity in presentation, and its clinical implications in terms of cardiovascular risk as well as considerations for therapy.…”