Vascular calcification in CKD: New insights into its mechanisms

Vascular calcification (VC) is a common complication of chronic kidney disease (CKD) and contributes to an increased risk of cardiovascular morbidity and mortality. However, effective therapies are still unavailable at present. It has been well established that VC associated with CKD is not a passive process of calcium phosphate deposition, but an actively regulated and cell‐mediated process that shares many similarities with bone formation. Additionally, numerous studies have suggested that CKD patients have specific risk factors and contributors to the development of VC, such as hyperphosphatemia, uremic toxins, oxidative stress and inflammation. Although research efforts in the past decade have greatly improved our knowledge of the multiple factors and mechanisms involved in CKD‐related VC, many questions remain unanswered. Moreover, studies from the past decade have demonstrated that epigenetic modifications abnormalities, such as DNA methylation, histone modifications and noncoding RNAs, play an important role in the regulation of VC. This review seeks to provide an overview of the pathophysiological and molecular mechanisms of VC associated with CKD, mainly focusing on the involvement of epigenetic modifications in the initiation and progression of uremic VC, with the aim to develop promising therapies for CKD‐related cardiovascular events in the future. Vascular calcification (VC) associated with chronic kidney disease (CKD) is caused by a combination of biochemical and physiological mechanisms, including not only the common pathophysiology of VC, but also CKD‐specific contributors. Epigenetic modifications, such as noncoding RNAs, DNA methylation and histone modifications, also play important roles in the initiation and progression of VC.