Functional vitamin K insufficiency, vascular calcification and mortality in advanced chronic kidney disease: A cohort study

Abstract

Patients with chronic kidney disease (CKD) suffer from vitamin K deficiency and are at high risk of vascular calcification (VC) and premature death. We investigated the association of functional vitamin K deficiency with all-cause mortality and whether this association is modified by the presence of VC in CKD stage 5 (CKD G5). Plasma dephosphorylated-uncarboxylated matrix Gla-protein (dp-ucMGP), a circulating marker of functional vitamin K deficiency, and other laboratory and clinical data were determined in 493 CKD G5 patients. VC was assessed in subgroups by Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC). Backward stepwise regression did not identify dp-ucMGP as an independent determinant of VC. During a median follow-up of 42 months, 93 patients died. Each one standard deviation increment in dp-ucMGP was associated with increased risk of all-cause mortality (sub-hazard ratio (sHR) 1.17; 95% confidence interval, 1.01–1.37) adjusted for age, sex, cardiovascular disease, diabetes, body mass index, inflammation, and dialysis treatment. The association remained significant when further adjusted for CAC and AVC in sub-analyses (sHR 1.22, 1.01–1.48 and 1.27, 1.01–1.60, respectively). In conclusion, functional vitamin K deficiency associates with increased mortality risk that is independent of the presence of VC in patients with CKD G5.

Matrix-GLA-Protein and Vascular Calcification: Can Diet Influence the Consequences of Matrix GLA Protein Inactivation? A Review

“…The protective effect of vitamin K 1 supplementation is particularly evident in dialysis patients. In such patients, both a reduction of dp-ucMGP plasma levels and reduced arterial stiffness could be achieved [114][115][116][117][118] .…”

“…The effects of reduced carboxylated MGP (cMGP) and γglutamyl carboxylase (GGCX) in atherosclerotic aortic plaques in the presence of reduced expression of vitamin K epoxide reductase complex, subunit 1-gene (Vkor-gen) could be at least partially ameliorated by a high-fat diet [138][139][140][141] .…”

Biological Role of Vitamin K—With Particular Emphasis on Cardiovascular and Renal Aspects

“…Dai et al conducted a cohort study on 493 patients in the stage G5 of CKD (CKD G5) [30]. The authors assessed the relationship between functional vitamin K deficiency and all-cause mortality as well as whether this relationship was modified by the presence of VC in stage 5 CKD.…”

Premature Aging in Chronic Kidney Disease: The Outcome of Persistent Inflammation beyond the Bounds

“…In addition, vitamin C and selenium are lost during dialysis treatment [82,85,86]. On the one hand, vitamin K can mitigate oxidative stress and prevent DNA damage, senescence, inflammation, and aging, which explains why vitamin K deficiency is associated with higher mortality risk in patients with CKD in stage 5 [86,87]. On the other hand, it may seem controversial to recommend physical activity to avoid oxidative stress.…”

“…Inflammation is maintained by moderate levels of pro-inflammatory mediators such as C-reactive protein (CRP) and cytokines [99] such as interleukin (IL)-6, IL-1, and TNFα [87,100,101]. As a biomarker of mortality, CRP level is superior to ferritin level and total white blood cell count and comparable to hypoalbuminemia [102].…”