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Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial.
Am J Kidney Dis. 2012 Feb; 59(2):186-95.AJ

Abstract

BACKGROUND

Vascular calcification is a predictor of cardiovascular morbidity and mortality. Hemodialysis patients experience severe vascular calcifications. Matrix Gla protein (MGP) is a central calcification inhibitor of the arterial wall; its activity depends on vitamin K-dependent γ-glutamate carboxylation. Uncarboxylated MGP, formed as a result of vitamin K deficiency, is associated with cardiovascular disease. Recent studies suggest poor vitamin K status in hemodialysis patients. We therefore aimed to investigate whether daily vitamin K supplementation improves the bioactivity of vitamin K-dependent proteins in hemodialysis patients, assessed by circulating dephosphorylated-uncarboxylated MGP, uncarboxylated osteocalcin, and uncarboxylated prothrombin (PIVKA-II [protein induced by vitamin K absence II]).

STUDY DESIGN

Interventional randomized non-placebo-controlled trial with 3 parallel groups.

SETTING & PARTICIPANTS

53 long-term hemodialysis patients in stable conditions, 18 years or older. 50 healthy age-matched individuals served as controls.

INTERVENTIONS

Menaquinone-7 (vitamin K(2)) treatment at 45, 135, or 360 μg/d for 6 weeks.

OUTCOMES

Plasma levels of dephosphorylated-uncarboxylated MGP, uncarboxylated osteocalcin, and PIVKA-II.

MEASUREMENTS

Plasma levels were assessed using enzyme-linked immunosorbent assays.

RESULTS

At baseline, hemodialysis patients had 4.5-fold higher dephosphorylated-uncarboxylated MGP and 8.4-fold higher uncarboxylated osteocalcin levels compared with controls. PIVKA-II levels were elevated in 49 hemodialysis patients. Vitamin K(2) supplementation induced a dose- and time-dependent decrease in circulating dephosphorylated-uncarboxylated MGP, uncarboxylated osteocalcin, and PIVKA-II levels. Response rates in the reduction in dephosphorylated-uncarboxylated MGP levels were 77% and 93% in the groups receiving 135 μg and 360 μg of menaquinone-7, respectively.

LIMITATIONS

Small sample size.

CONCLUSIONS

This study confirms that most hemodialysis patients have a functional vitamin K deficiency. More importantly, it is the first study showing that inactive MGP levels can be decreased markedly by daily vitamin K(2) supplementation. Our study provides the rationale for intervention trials aimed at decreasing vascular calcification in hemodialysis patients by vitamin K supplementation.

Links

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Authors+Show Affiliations

Westenfeld R
Division of Cardiology, Pulmonary Diseases, Vascular Medicine, University Hospital Düsseldorf, Germany.
Krueger T
No affiliation info available
Schlieper G
No affiliation info available
Cranenburg EC
No affiliation info available
Magdeleyns EJ
No affiliation info available
Heidenreich S
No affiliation info available
Holzmann S
No affiliation info available
Vermeer C
No affiliation info available
Jahnen-Dechent W
No affiliation info available
Ketteler M
No affiliation info available
Floege J
No affiliation info available
Schurgers LJ
No affiliation info available

MeSH

AdultAgedAged, 80 and overBiomarkersCalcium-Binding ProteinsComorbidityDietary SupplementsDisease ProgressionDose-Response Relationship, DrugExtracellular Matrix ProteinsFemaleHumansKidney DiseasesMaleMiddle AgedOsteocalcinProspective StudiesProtein PrecursorsProthrombinRenal DialysisSingle-Blind MethodTreatment OutcomeVascular CalcificationVitamin K 2Vitamin K Deficiencyalpha-2-HS-Glycoprotein

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

22169620

Clinical Trial Links

Clinical trial which this article describes
Vitamin K2 Supplementation and Vascular Calcification
Vitamin K Supplementation in Patients on Hemodialysis

Citation

Westenfeld, Ralf, et al. "Effect of Vitamin K2 Supplementation On Functional Vitamin K Deficiency in Hemodialysis Patients: a Randomized Trial." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 59, no. 2, 2012, pp. 186-95.
Westenfeld R, Krueger T, Schlieper G, et al. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis. 2012;59(2):186-95.
Westenfeld, R., Krueger, T., Schlieper, G., Cranenburg, E. C., Magdeleyns, E. J., Heidenreich, S., Holzmann, S., Vermeer, C., Jahnen-Dechent, W., Ketteler, M., Floege, J., & Schurgers, L. J. (2012). Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 59(2), 186-95. https://doi.org/10.1053/j.ajkd.2011.10.041
Westenfeld R, et al. Effect of Vitamin K2 Supplementation On Functional Vitamin K Deficiency in Hemodialysis Patients: a Randomized Trial. Am J Kidney Dis. 2012;59(2):186-95. PubMed PMID: 22169620.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. AU - Westenfeld,Ralf, AU - Krueger,Thilo, AU - Schlieper,Georg, AU - Cranenburg,Ellen C M, AU - Magdeleyns,Elke J, AU - Heidenreich,Stephan, AU - Holzmann,Stefan, AU - Vermeer,Cees, AU - Jahnen-Dechent,Willi, AU - Ketteler,Markus, AU - Floege,Jürgen, AU - Schurgers,Leon J, Y1 - 2011/12/09/ PY - 2011/04/29/received PY - 2011/10/06/accepted PY - 2011/12/16/entrez PY - 2011/12/16/pubmed PY - 2012/3/23/medline SP - 186 EP - 95 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 59 IS - 2 N2 - BACKGROUND: Vascular calcification is a predictor of cardiovascular morbidity and mortality. Hemodialysis patients experience severe vascular calcifications. Matrix Gla protein (MGP) is a central calcification inhibitor of the arterial wall; its activity depends on vitamin K-dependent γ-glutamate carboxylation. Uncarboxylated MGP, formed as a result of vitamin K deficiency, is associated with cardiovascular disease. Recent studies suggest poor vitamin K status in hemodialysis patients. We therefore aimed to investigate whether daily vitamin K supplementation improves the bioactivity of vitamin K-dependent proteins in hemodialysis patients, assessed by circulating dephosphorylated-uncarboxylated MGP, uncarboxylated osteocalcin, and uncarboxylated prothrombin (PIVKA-II [protein induced by vitamin K absence II]). STUDY DESIGN: Interventional randomized non-placebo-controlled trial with 3 parallel groups. SETTING & PARTICIPANTS: 53 long-term hemodialysis patients in stable conditions, 18 years or older. 50 healthy age-matched individuals served as controls. INTERVENTIONS: Menaquinone-7 (vitamin K(2)) treatment at 45, 135, or 360 μg/d for 6 weeks. OUTCOMES: Plasma levels of dephosphorylated-uncarboxylated MGP, uncarboxylated osteocalcin, and PIVKA-II. MEASUREMENTS: Plasma levels were assessed using enzyme-linked immunosorbent assays. RESULTS: At baseline, hemodialysis patients had 4.5-fold higher dephosphorylated-uncarboxylated MGP and 8.4-fold higher uncarboxylated osteocalcin levels compared with controls. PIVKA-II levels were elevated in 49 hemodialysis patients. Vitamin K(2) supplementation induced a dose- and time-dependent decrease in circulating dephosphorylated-uncarboxylated MGP, uncarboxylated osteocalcin, and PIVKA-II levels. Response rates in the reduction in dephosphorylated-uncarboxylated MGP levels were 77% and 93% in the groups receiving 135 μg and 360 μg of menaquinone-7, respectively. LIMITATIONS: Small sample size. CONCLUSIONS: This study confirms that most hemodialysis patients have a functional vitamin K deficiency. More importantly, it is the first study showing that inactive MGP levels can be decreased markedly by daily vitamin K(2) supplementation. Our study provides the rationale for intervention trials aimed at decreasing vascular calcification in hemodialysis patients by vitamin K supplementation. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/22169620/Effect_of_vitamin_K2_supplementation_on_functional_vitamin_K_deficiency_in_hemodialysis_patients:_a_randomized_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(11)01570-8 DB - PRIME DP - Unbound Medicine ER -