Role of Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (MBD) in the Pathogenesis of Cardiovascular Disease in CKD

J Atheroscler Thromb. 2023 Aug 1;30(8):835-850. doi: 10.5551/jat.RV22006. Epub 2023 May 30.

Abstract

Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Multiple factors account for the increased incidence of cardiovascular morbidity and mortality in patients with CKD. Traditional risk factors for atherosclerosis and arteriosclerosis, including age, hypertension, dyslipidemia, diabetes mellitus, and smoking, are also risk factors for CKD. Non-traditional risk factors specific for CKD are also involved in CVD pathogenesis in patients with CKD. Recently, CKD-mineral and bone disorder (CKD-MBD) has emerged as a key player in CVD pathogenesis in the context of CKD. CKD-MBD manifests as hypocalcemia and hyperphosphatemia in the later stages of CKD; however, it initially develops much earlier in disease course. The initial step in CKD-MBD involves decreased phosphate excretion in the urine, followed by increased circulating concentrations of fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH), which increase urinary phosphate excretion. Simultaneously, the serum calcitriol concentration decreases as a result of FGF23 elevation. Importantly, FGF23 and PTH cause left ventricular hypertrophy, arrhythmia, and cardiovascular calcification. More recently, calciprotein particles, which are nanoparticles composed of calcium, phosphate, and fetuin-A, among other components, have been reported to cause inflammation, cardiovascular calcification, and other clinically relevant outcomes. CKD-MBD has become one of the critical therapeutic targets for the prevention of cardiovascular events and is another link between cardiology and nephrology. In this review, we describe the role of CKD-MBD in the pathogenesis of cardiovascular disorders and present the current treatment strategies for CKD-MBD.

Keywords: CKD; CKD–MBD; Calcium; Cardiovascular disease; Phosphate.

Publication types

  • Review

MeSH terms

  • Atherosclerosis* / pathology
  • Cardiovascular Diseases* / etiology
  • Cardiovascular Diseases* / metabolism
  • Chronic Kidney Disease-Mineral and Bone Disorder* / complications
  • Disease Progression
  • Humans
  • Minerals
  • Parathyroid Hormone
  • Phosphates
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / metabolism

Substances

  • Parathyroid Hormone
  • Phosphates
  • Minerals