Review Volume 11, Issue 12 pp 4274—4299

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

Carla Viegas1,2, , Nuna Araújo1, , Catarina Marreiros1, , Dina Simes1,2, ,

  • 1 Centre of Marine Sciences (CCMAR), University of Algarve, Faro 8005-139, Portugal
  • 2 GenoGla Diagnostics, Centre of Marine Sciences (CCMAR), University of Algarve, Faro 8005-139, Portugal

Received: April 11, 2019       Accepted: June 17, 2019       Published: June 26, 2019
How to Cite

Copyright: Viegas et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Chronic kidney disease (CKD) is one of the most powerful predictors of premature cardiovascular disease (CVD), with heightened susceptibility to vascular intimal and medial calcification associated with a high cardiovascular mortality. Abnormal mineral metabolism of calcium (Ca) and phosphate (P) and underlying (dys)regulated hormonal control in CKD-mineral and bone disorder (MBD) is often accompanied by bone loss and increased vascular calcification (VC). While VC is known to be a multifactorial process and a major risk factor for CVD, the view of primary triggers and molecular mechanisms complexity has been shifting with novel scientific knowledge over the last years. In this review we highlight the importance of calcium-phosphate (CaP) mineral crystals in VC with an integrated view over the complexity of CKD, while discuss past and recent literature aiming to highlight novel horizons on this major health burden. Exacerbated VC in CKD patients might result from several interconnected mechanisms involving abnormal mineral metabolism, dysregulation of endogenous calcification inhibitors and inflammatory pathways, which function in a feedback loop driving disease progression and cardiovascular outcomes. We propose that novel approaches targeting simultaneously VC and inflammation might represent valuable new prognostic tools and targets for therapeutics and management of cardiovascular risk in the CKD population.


CKD: Chronic kidney disease; CVD: Cardiovascular disease; Ca: Calcium; P: Phosphate; MBD: Mineral and bone disorder; VC: Vascular calcification; CaP: Calcium-phosphate mineral; GFR: Glomerular filtration rate; VSMCs: Vascular smooth muscle cells; ECM: Extracellular matrix; EVs: Extracellular vesicles; PBs: Phosphate binders; PTH: Parathyroid hormone; 1,25D: 1,25 vitamin D; CaSR: Calcium-sensing receptors; FGF-23: Fibroblast growth factor 23; SHPT: Secondary hyperparathyroidism; VKDPs: Vitamin K-dependent proteins; Glu: Glutamic acid; Gla: γ-carboxyglutamic acid; MGP: Matrix Gla protein; CBPBs: Calcium-based phosphate binders; KDIGO: Kidney Disease Outcomes Quality Initiative Guidelines; CPPs: Calciprotein p-articles; GRP: Gla-rich protein; MGP-/-: Knockout mice for MGP; GRP-/-: Knockout mice for GRP; CPP-I: Primary calciprotein particles; CPP-II: Secondary calciprotein particles; BMP2: Bone morphogenetic protein 2; Dp-ucMGP: Dephosphorylated and uncarboxylated matrix Gla protein; CRP: C-reactive protein; IL: Interleukin; TNF-α: Tumor necrosis factor alpha; BCP: Basic calcium phosphate; SASP: Senescence-associated secretory phenotype.