Vitamin k1 and Its Relation to Vascular Calcification in Hemodialysis Patients

September 28, 2021 updated by: Alshaimaa Sayed Hassan Mubarak, Assiut University

Vitamin k Status and Its Relation to Vascular Calcification in Hemodialysis Patients in Assiut University Hospital

Vascular calcification (VC) represents one of the major complications associated with progressive renal impairment. Matrix Gla-protein (MGP) is a vitamin K-dependent protein that acts as a powerful inhibitor of vascular calcification. Despite this fact, it remains unknown whether supplementation with vitamin K can lead to reduction or reversal of vascular and heart valve calcification. Our study aims primarily to investigate the effect of intravenous vitamin K1 three times weekly for a total duration of 6 months on the serum levels of dephosphorylated-uncarboxylated MGP (dp-ucMGP) as well as aortic calcification score and severity of aortic and mitral valve lesions.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Vascular calcification (VC) represents one of the major complications associated with progressive renal impairment. In addition, VC has been regarded as one of the major predictors of cardiovascular risk, the most common cause of mortality in chronic kidney disease patients (CKD).

65% of end-stage kidney disease (ESKD) patients on regular peritoneal dialysis (PD) and 80-85% of ESKD patients on regular hemodialysis (HD) showed coronary or aortic calcification. These calcifications were associated with the total time on dialysis, with a yearly-increase of vascular calcification by 15% . Traditional risk factors for vascular calcification include age, male gender, smoking, diabetes, hypertension, and dyslipidemia.

VC, the pathological deposition of mineral in the vascular system, can manifest as intimal, medial, or heart valve calcification. Whereas intimal calcification, taking place within atherosclerotic plaque in aorta and coronary arteries, indicates advanced atherosclerosis, media calcification, which is often found in patients with diabetes and/or CKD, is characterized by diffuse mineral deposition along elastic fibers in both low resistance elastic-type as well as high resistance muscle-type arteries. Calciphylaxis, or calcific uremic arteriolopathy, represents a special form of ectopic, extraosseous calcification, that is characteristically observed in CKD patients, particularly those with ESKD with additional secondary hyperparathyroidism or those receiving warfarin. A study on hemodialysis patients showed more than two-fold higher odds of aortic and iliac calcifications in patients receiving warfarin than those who do not . VC results from an imbalance of promoters and inhibitors. Matrix Gla-protein (MGP) is a vitamin K-dependent protein and has been found to be expressed by medial vascular smooth muscles of arteries, endothelial cells, chondroblasts, and fibroblasts. Moreover, it is also expressed in the heart, kidneys, and lungs . MGP acts as a powerful inhibitor of vascular calcification. Loss-of-function mutations of MGP was associated with vascular calcification in animal models. In the setting of progressive vascular calcification, MGP transcription increases, giving rise to dephosphorylated-uncarboxylated MGP (dp-ucMGP). This molecule represents the inactive form of MGP, which later undergoes a γ- glutamate carboxylation and serine phosphorylation to produce the active form, phosphorylated carboxylated MGP (p- cMGP). Vitamin K acts as a cofactor for the enzyme γ-glutamylcarboxylase that is responsible for activating dp-ucGMP into dp-cMGP. Despite its key role in activation of dp-ucMGP, it remains unknown whether supplementation with vitamin K can lead to reduction or reversal of vascular and heart valve calcification in hemodialysis patients.

Study Type

Interventional

Enrollment (Actual)

120

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Assiut, Egypt, 71515
        • Assiut University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males or females ≥18 years of age,
  • Not less than 6 months on HD,
  • High level of serum dephosphorylated uc-MGP
  • Signed informed consent,

Exclusion Criteria:

  • Patients with normal level of dp-ucMGP
  • History of thrombosis,
  • Intake of vitamin K antagonists (warfarin) at baseline or in the 3 months prior to baseline,
  • Inflammatory bowel disease,
  • Liver dysfunction,

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hemodialysis patient with high level of dp uc-MGP
one hundred and twenty hemodialysis patients with high level of dephosphorylated uc-MGP received 5 mg of oral vitamin K1 (phylloquinone) three times /week for 6 months at the end of HD session. We measured the serum dephosphorylated- uncarboxylated matrix Gla protein (dp-ucMGP) 6 months after vitamin K1 supplementation. In addition, plain lateral abdominal x-ray was conducted prior to and after 6 months of vitamin K supplementation to assess lumbar aorta calcification. The extent of aortic calcification score (AAC) was assessed by Kauppila score.In addition, study patients were subjected to an echocardiography at baseline as well as 6 months post vitamin K1 supplementation. Echocardiography was performed by the same operator.
Drug: oral vitamin k1 (phylloquinone)
The enrolled patients received 5 mg of oral vitamin K1 (phylloquinone) three times /week for 6 months at the end of HD session to ensure compliance. We measured the serum dephosphorylated- uncarboxylated matrix Gla protein (dp-ucMGP) before and 6 months after vitamin K1 supplementation. In addition, plain lateral abdominal x-ray was conducted prior to and after 6 months of vitamin K supplementation to assess lumbar aorta calcification. The extent of aortic calcification score (AAC) was assessed by a semi-quantitative grading system developed by Kauppila.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of vitamin k1 supplementation on vascular calcification
Time Frame: 6 months
Our study aims primarily to investigate the effect of oral vitamin K1 three times weekly for a total duration of 6 months on the serum levels of dephosphorylated-uncarboxylated MGP (dp-ucMGP) as well as aortic calcification score and severity of aortic and mitral valve lesions.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2018

Primary Completion (Actual)

July 30, 2019

Study Completion (Actual)

January 1, 2020

Study Registration Dates

First Submitted

September 19, 2021

First Submitted That Met QC Criteria

September 19, 2021

First Posted (Actual)

September 29, 2021

Study Record Updates

Last Update Posted (Actual)

October 5, 2021

Last Update Submitted That Met QC Criteria

September 28, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • vit k in hemodialysis patient

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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