High Dephosphorylated-Uncarboxylated MGP in Hemodialysis patients: risk factors and response to vitamin K 2, A pre-post intervention clinical trial

BMC Nephrol. 2017 Jun 7;18(1):191. doi: 10.1186/s12882-017-0609-3.

Abstract

Background: Vascular calcifications are highly prevalent in hemodialysis patients. Dephosphorylated-uncarboxylated MGP (dp-ucMGP) was found to increase in vitamin K-deficient patients and may be associated with vascular calcifications. Supplementation of hemodialysis patients with vitamin K2 (menaquinone-7) has been studied in Europe with a maximum 61% drop of dp-ucMGP levels. The aim of this study is to assess first the drop of dp-ucMGP in an Eastern Mediterranean cohort after vitamin K2 treatment and second the correlation between baseline dp-ucMGP and vascular calcification score.

Methods: This is a prospective, pre-post intervention clinical trial involving 50 hemodialysis patients who received daily 360 μg of menaquinone-7 for 4 weeks. At baseline they were assessed for plasma dp-ucMGP levels and vascular calcification scores (AC-24) as well as for other demographic, clinical and biological variables. Dp-ucMGP levels were measured a second time at 4 weeks.

Results: At baseline, dp-ucMGP levels were extremely elevated with a median of 3179.15 (1825.25; 4339.50) pM and correlated significantly with AC-24 (Spearman's rho = 0.43, P = 0.002). Using a bivariate regression analysis, the association between dp-ucMGP levels and AC-24 was most significant when comparing dp-ucMGP levels less than 1000 to those more than 1000 pM (P = 0.02). Dp-ucMGP levels higher than 5000 pM were significantly associated with females, patients with recent fracture and patients with lower serum albumin (respectively P = 0.02, 0.004 and 0.046). The average drop of dp-ucMGP at 4 weeks of treatment was found to be 86% with diabetics having the lowest drop rate (P = 0.01).

Conclusion: Vitamin K deficiency, as assessed by high dp-ucMGP levels, is profound in hemodialysis patients from the Eastern Mediterranean region and it is significantly correlated with vascular calcifications. Daily 360 μg of menaquinone-7, given for 4 weeks, effectively reduces dp-ucMGP in this population. Future studies are needed to assess the changes in vascular calcifications in hemodialysis patients treated with vitamin K2 over a longer follow-up period.

Trial registration: The clinical trial was registered on clinicaltrials.gov (Identification number NCT02876354 , on August 11, 2016).

Keywords: Dephosphorylated Uncarboxylated matrix Gla protein; Hemodialysis; Menaquinone-7; Pre-post intervention clinical trial; Vascular calcifications; Vitamin K2.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Calcium-Binding Proteins / blood*
  • Extracellular Matrix Proteins / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phosphorylation / physiology
  • Prospective Studies
  • Renal Dialysis / adverse effects*
  • Renal Dialysis / trends
  • Risk Factors
  • Treatment Outcome
  • Vitamin K 2 / therapeutic use*
  • Vitamin K Deficiency / blood*
  • Vitamin K Deficiency / drug therapy*
  • Vitamin K Deficiency / etiology

Substances

  • Biomarkers
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • matrix Gla protein
  • Vitamin K 2

Associated data

  • ClinicalTrials.gov/NCT02876354