Abstract
BackgroundVascular 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.MethodsThis 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.ResultsAt 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).ConclusionVitamin 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 registrationThe clinical trial was registered on clinicaltrials.gov (Identification number NCT02876354, on August 11, 2016).
Highlights
Vascular calcifications are highly prevalent in hemodialysis patients
The majority of patients reaching end-stage renal disease (ESRD) and dialysis suffer from vascular calcifications (VC) and are at an increased risk of mortality [1,2,3]
Median body mass index (BMI) was 25.82 (22.85; 28.42) Kg/ m2. 4% were on cinacalcet and 40% on non-calciumbased phosphate binders
Summary
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. In hemodialysis (HD) patients, factors inducing VC are numerous They include the traditional ones such as age, smoking, diabetes, hypertension, hyperlipidemia and those specific to chronic kidney disease (CKD) such as hyperparathyroidism and hyperphosphatemia. In order to lower or prevent VC in CKD patients, many interventions have been studied in the past, such as statins, non-calcium-based phosphate binders and calcimimetics. None of these interventions proved to have a solid and consistent beneficial effect on VC [6,7,8,9]
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