In Chronic Kidney Disease, vascular calcification (VC) is highly prevalent even at early
stages and is gradually enhanced, along with disease progression to End-Stage Renal Disease (ESRD).
The calcification pattern in uremia includes all types of mineralization and contributes to the heavy
cardiovascular (CV) burden that is common in these patients. Ectopic mineralization is the result of the
imbalance between inhibitors and promoters of vascular calcification, with the latter overwhelming the
former. The most powerful, natural inhibitor of calcification is Matrix Gla Protein (MGP), a small vitamin
K dependent protein, secreted by chondrocytes and vascular smooth muscle cells. In uremia, MGP
was reported as the only molecule able to reverse VC by “sweeping” calcium and hydroxyapatite crystals
away from the arterial wall. To become biologically active, this protein needs to undergo carboxylation
and phosphorylation, reactions highly dependent on vitamin K status. The inactive form of MGP
reflects the deficiency of vitamin K and has been associated with CV events and mortality in ESRD
patients. During the past decade, vitamin K status has emerged as a novel risk factor for vascular calcification
and CV disease in various populations, including dialysis patients. This review presents evidence
regarding the association between vitamin K and CV disease in ESRD patients, which are prone
to atherosclerosis and atheromatosis.