Underlying Causes of Low Vitamin K Status in Hemodialysis Patients
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Copenhagen
- Enrollment
- 33
- Locations
- 2
- Primary Endpoint
- Δ-dp-uc-MGP (Sub-trial 5)
Study Overview
Brief Summary
Studies have shown that patients with chronic kidney disease in hemodialysis have a low vitamin K status which is believed to be related to an increased risk of atherosclerosis and increased bleeding tendency. The underlying causes of low vitamin K status in hemodialysis patients is unknown. Thus, the aim of this study is to investigate why hemodialysis patients have a low vitamin K status and how to improve it.
This study is composed of five trials. Four of them are based on possible hypotheses to the low vitamin K status. The hypotheses are:
- The daily intake of vitamin K is insufficient.
- Vitamin K is removed from the blood during dialysis.
- Absorption in the intestines is impaired.
- The analysis method (dephosphorylated-uncarboxylated MGP) is influenced by the patients' protein intake.
The purpose of the fifth trial is to investigate solutions to improve the vitamin K status of hemodialysis. One is to improve vitamin K status through diet with an increased focus on foods with high concentrations of vitamin K while considering phosphate, potassium and fluid restrictions. The second is to increase vitamin K status through a daily supplement of 360µg Menakinon-7.
Detailed Description
Studies have reported a low vitamin K status in chronic kidney disease patients in hemodialysis linked to an increased risk of atherosclerosis and increased bleeding tendency. The overall aim of this study is to investigate the underlying causes of the reported low vitamin K status and to improve the patients' vitamin K status through diet and supplement. The study is divided in 5 sub-trials listed below. Sub-trial 1-4 focuses on determining the underlying course of low vitamin K status while sub-trial 5 deals with possible solutions to the reported low vitamin K status.
The analysis method used to determine vitamin K status is dephosphorylated-uncarboxylated Matrix-Gla-Protein (dp-ucMGP). Dp-ucMGP is the inactive form of the protein MGP whose activation is vitamin K dependent. The dp-ucMGP analysis method is not a direct measure of vitamin K status. However, an increased concentration of dp-ucMGP is a manifestation of a low vitamin K status and vice versa.
Sub-trial 1: Intake of vitamin K Aim: To assess the patients' intake of vitamin K. Hypothesis: The daily intake of vitamin K is insufficient. Method: Patients are asked to fill out a food frequency questionnaire (FFQ). The FFQ is based on their intake of different foods rich in vitamin K during the last month. To compare the results from the FFQ with their actual vitamin K status a blood sample is collected and analyzed to determine dp-ucMGP. Participants: 30.
Sub-trial 2: The influence of dialysis Aim: To examine whether vitamin K status is compromised during dialysis. Hypothesis: Vitamin K is removed from the blood during dialysis. Method: A blood test is collected before and after dialysis and analyzed to determine dp-ucMGP. At the end of the dialysis a sample of the remaining dialysis-water is collected and analyzed to determine dp-ucMGP. Furthermore, the patients will be weighed before and after dialysis with the purpose of calculating concentrations. Participants: 16 (the analysis of the dialysis water is done for five patients at first, if the results are useful the analysis is done for every participant).
Sub-trial 3: Absorption Aim: To investigate whether a decreased absorption can be the cause of the low vitamin K status. Hypothesis: Absorption in the intestines is impaired. Method: A D-xylose test is performed. The participants are given a dose of 15g D-xylose dissolved in water and after one hour a sample of blood is collected to determine D-xylose in serum. Prior to this trial the patients need to be fasting.The patients are asked to fill out a FFQ concerning their intake of fat during the last month. Participants: 16
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Supportive Care
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Chronic kidney disease
- •Hemodialysis (> 3 months) at Herlev Hospital, Nephrological department
- •Understands and are able to read danish
- •Able to collaborate on diet etc.
Exclusion Criteria
- •Warfarin treatment
- •Pregnant or breastfeeding
- •Prior intake of vitamin K supplements
- •Short bowl disease, pancreatitis or other malabsorption diseases/syndromes
- •Diabetes Mellitus (only an exclusion criterion in sub-trial 3: Absorption of vitamin K)
Arms & Interventions
Menakinon-7
Menakinon-7 360 µg tablet by mouth, every day for 6 weeks
Intervention: Menakinon 7 (Dietary Supplement)
Diet with vitamin K
Diet rich in vitamin K for 6 weeks
Intervention: Diet rich in vitamin K (Dietary Supplement)
Outcomes
Primary Outcomes
Δ-dp-uc-MGP (Sub-trial 5)
Time Frame: 15 weeks
Comparison of concentration of dp-ucMGP in blood samples through out the intervention
Secondary Outcomes
- dp-ucMGP status (Sub-trial 1)(1 day)
- Vitamin K intake (Sub-trial 1)(1 month)
- dp-ucMGP concentration in dialysis water (Sub-trial 2)(1 day)
- Δ-concentration of dp-ucMGP (Sub-trial 2)(1 day)
- Δ-weight (Sub-trial 2)(1 day)
- Concentration of D-xylose (Sub-trial 3)(1 day)
- Fat in the diet (Sub-trial 3)(1 day)
- Δ-dp-uc-MGP (Sub-trial 4)(14 day)
- Protein in the diet (Sub-trial 4)(14 days)
- Calcification (Sub-trial 5)(15 weeks)
- Quality of life (Sub-trial 5)(15 weeks)
- The patient's perception of the presence of bruises (Sub-trial 5)(15 weeks)
- Δ-factor 2, 7,10 concentration (Sub-trial 5)(15 weeks)
Investigators
Jens Rikardt Andersen
Associate Professor
University of Copenhagen