Mechanistic insights into CKD-MBD-related vascular calcification and its clinical implications

Life Sci. 2022 Dec 15;311(Pt B):121148. doi: 10.1016/j.lfs.2022.121148. Epub 2022 Nov 3.


Chronic Kidney Disease (CKD) is linked to a rising prevalence of morbidity and mortality primarily from cardiovascular complications and is considered a high or very high-risk associated cardiovascular state. These poor outcomes are associated with CKD-mineral and bone disorders (CKD-MBD) in CKD patients, which are manifested by vascular calcification. Patients with chronic renal illness have not only accelerated intimal and medial calcification, but heart valves, and possibly the myocardium get also calcified, as well as the uncommon state of calcific uremic arteriolopathy (calciphylaxis). So the CKD-MBD associated vascular calcification might be a key mediator for an array of cardiovascular sequelae. Various routes link vascular calcification with CKD including the involvement of non-traditional risk factors but still, mechanisms are incompletely understood, and focused treatments have been slow to emerge. Major events and factors in vascular calcification involve the conversion of vascular smooth muscles cells into chondrocyte-like cells. Further dysregulation of calcium, phosphate, parathyroid hormone (PTH), Vitamin D hormonal system, phosphorous, and imbalance of promoters and inhibitors (Fetuin-A and Vitamin K dependent matrix Gla protein) plays the important role in promoting CKD-MBD associated vascular calcification. Fibroblast growth factor-23 (FGF-23), Sclerostin, and Klotho are thought to be the emerging factors involved in the CKD-MBD leading to vascular calcification process and cardiovascular mortality. This review summarizes the brief pathological basis of vascular calcification in CKD, current and emerging approaches including the vast arrangement of contributors and inhibitors for the early identification and treatment.

Keywords: CKD-MBD; Calcium; Chronic kidney disease; Phosphate; Vascular calcification.

Publication types

  • Review

MeSH terms

  • Bone Diseases / complications
  • Bone Diseases / metabolism
  • Chronic Kidney Disease-Mineral and Bone Disorder* / complications
  • Fibroblast Growth Factors
  • Humans
  • Parathyroid Hormone / metabolism
  • Phosphates / metabolism
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / metabolism
  • Vascular Calcification* / etiology
  • Vascular Calcification* / pathology


  • Fibroblast Growth Factors
  • Parathyroid Hormone
  • Phosphates