High Dephosphorylated-Uncarboxylated MGP in Hemodialysis patients: risk factors and response to vitamin K2, A pre-post intervention clinical trial

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, Pre-post intervention clinical trial, Hemodialysis,

Menaquinone-7, Vascular calcifications, Vitamin K2