Despite many advances in the care of patients with chronic kidney disease (CKD) and ESKD, cardiovascular (CV) disease remains the leading cause of death in the kidney disease patient population. One of the factors explaining this excess mortality risk is vascular calcification, which predisposes patients to myocardial ischemia, left ventricular hypertrophy, and stroke (1).
The pathophysiology of vascular calcification in patients with CKD and ESKD is distinct from that in the general population. In the general population, vascular calcifications form in the intima of vessels and are linked to traditionally modifiable risk factors, including smoking, age, obesity, diabetes, hypertension, and hypercholesterolemia. By contrast, in CKD and ESKD, vascular calcifications form in the intima and media of medium and large arteries. Whereas the pathogenesis of intimal vascular calcification in CKD and ESKD mirrors that of the general population, the pathogenesis of medial vascular calcification is not well understood.
Medial vascular calcification occurs early in the course of CKD (2) and strongly predicts cardiovascular (CV) events and mortality. Mineral–bone disorder is a major factor involved in the development of medial vascular calcification (3, 4). Other involved factors include vascular smooth muscle cell osteochondrogenic shift (4), decreased levels of calcification inhibitors (5, 6), and increased levels of oxidative stress, all of which contribute to the progression of vascular calcification. Medial vascular calcification is a highly regulated multipathway process (4), but there are not yet any proven preventative treatments. Vitamin K supplementation is one potential therapy that is currently being investigated in clinical trials.
Baber U, et al. Coronary plaque composition, morphology, and outcomes in patients with and without chronic kidney disease presenting with acute coronary syndromes. JACC Cardiovasc Imaging 2012; 5:S53–S61.
Fang Y, et al. Early chronic kidney disease–mineral bone disorder stimulates vascular calcification. Kidney Int 2014; 85:142–150.
Li X, Giachelli CM. Sodium-dependent phosphate cotransporters and vascular calcification. Curr Opin Nephrol Hypertens 2007; 16:325–328.
Schafer C, et al. The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest 2003; 112:357–366.
Suliman ME, et al. Vascular calcification inhibitors in relation to cardiovascular disease with special emphasis on fetuin-A in chronic kidney disease. Adv Clin Chem 2008; 46:217–262.
Cranenburg EC, et al. Uncarboxylated matrix Gla protein (ucMGP) is associated with coronary artery calcification in haemodialysis patients. Thromb Haemost 2009; 101:359–366.
Schurgers LJ, et al. The circulating inactive form of matrix Gla protein is a surrogate marker for vascular calcification in chronic kidney disease: A preliminary report. Clin J Am Soc Nephrol 2010; 5:568–575.
Schlieper G, et al. Circulating nonphosphorylated carboxylated matrix Gla protein predicts survival in ESKD. J Am Soc Nephrol 2011; 22:387–395.
Fusaro M, et al. Vitamin K, vertebral fractures, vascular calcifications, and mortality: Vitamin K Italian (VIKI) dialysis study. J Bone Miner Res 2012; 27:2271–2278.
Delanaye P, et al. Dephosphorylated-uncarboxylated matrix Gla protein concentration is predictive of vitamin K status and is correlated with vascular calcification in a cohort of hemodialysis patients. BMC Nephrol 2014; 15:145.
Meuwese CL, et al. Associations between thyroid hormones, calcification inhibitor levels and vascular calcification in end-stage renal disease. PLoS One 2015; 10:e0132353.
Thamratnopkoon S, et al. Correlations of plasma desphosphorylated uncarboxylated matrix Gla protein with vascular calcification and vascular stiffness in chronic kidney disease. Nephron 2017; 135:167–172.
Westenfeld R, et al. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: A randomized trial. Am J Kidney Dis 2012; 59:186–195.
Caluwe R, et al. Vitamin K2 supplementation in haemodialysis patients: A randomized dose-finding study. Nephrol Dial Transplant 2014; 29:1385–1390.