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

PLoS One. 2021 Feb 24;16(2):e0247623. doi: 10.1371/journal.pone.0247623. eCollection 2021.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Calcium-Binding Proteins / blood
  • Cohort Studies
  • Extracellular Matrix Proteins / blood
  • Female
  • Humans
  • Male
  • Matrix Gla Protein
  • Middle Aged
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / mortality
  • Renal Insufficiency, Chronic / pathology
  • Survival Rate
  • Vascular Calcification / blood
  • Vascular Calcification / complications*
  • Vascular Calcification / mortality
  • Vascular Calcification / pathology
  • Vitamin K / blood*
  • Vitamin K Deficiency / blood
  • Vitamin K Deficiency / complications*
  • Vitamin K Deficiency / mortality
  • Vitamin K Deficiency / pathology

Substances

  • Biomarkers
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • Vitamin K

Grants and funding

The study benefited from generous support from Strategic Research Program in Diabetes at Karolinska Institutet (Swedish Research Council grant No 2009-1068), European Union's Horizon 2020 research and innovation Program under the Marie Skłodowska-Curie grant agreement No 722609; www.intricare.eu), Heart and Lung Foundation (PS), CIMED (PS), Njurfonden (PS), and Westmans Foundation (PS). HSJ is supported by an ERA-EDTA long-term fellowship. Baxter Novum is the result of a grant from Baxter Healthcare corporation to Karolinska Institutet. Baxter Healthcare Corporation provided support in the form of salaries for BL, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.