Evaluating the Vitamin K2 Status of Calcium-based Stone Formers
Study Details
Study Description
Brief Summary
This is an observation, single site-study with one study visit during which all data and samples will be collected. Study participants will be asked to provide blood, urine, and fecal samples so that the investigators may study the differences in the gut microbiota, vitamin K2 levels, and other parameters between participants who form kidney stones and those who do not.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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Detailed Description
It is hypothesized that calcium-based stone formers will have an altered fecal gut microbiota compared to non-stone former controls. This altered microbiota will have a lower abundance of bacteria that produce menaquinones (vitamin K2), thus stone formers will also have a different blood menaquinone profile compared to controls. Ultimately, the different levels of menaquinones will result in increased inactive Matrix Gla protein (dp-ucMGP), which is a key protein that sequesters free calcium. To test this hypothesis, calcium-based stone former and non-stone forming controls will be recruited to a single site, observation study to collect urine, blood, and fecal samples. These samples will be used to determine dp-ucMGP levels, menaquinone profiles, the composition of the gut microbiota, and other parameters of interest.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Stone Formers Individuals who have experienced at least one incidence of calcium-based kidney stones in the last 12 months |
|
| Controls Individuals who have never had a kidney stone in their lifetime. |
Outcome Measures
Primary Outcome Measures
- Fecal microbiota composition of stone-formers and controls [At baseline only]
Fecal samples will be collected using out validated toilet paper method. Microbial DNA will be extracted and sequenced using next-generation sequencing.
- Concentration of urine dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein) [At baseline only]
dp-ucMGP will be quantified using an enzyme-linked immunosorbent assay
- Concentration of blood dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein) [At baseline only]
dp-ucMGP will be quantified using an enzyme-linked immunosorbent assay
- Concentration of blood total osteocalcin (OC) [At baseline only]
Total OC will be quantified using an enzyme-linked immunosorbent assay
- Concentration of blood undercarboxylated osteocalcin (ucOC) [At baseline only]
ucOC will be quantified using an enzyme-linked immunosorbent assay
- Concentration of urine total osteocalcin (OC) [At baseline only]
Total OC will be quantified using an enzyme-linked immunosorbent assay
- Concentration of urine undercarboxylated osteocalcin (ucOC) [At baseline only]
ucOC will be quantified using an enzyme-linked immunosorbent assay
- Concentration of blood menaquinones (vitamin K2) - MK-4 [At baseline only]
Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
- Concentration of blood menaquinones (vitamin K2) - MK-7 [At baseline only]
Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
- Concentration of blood menaquinones (vitamin K2) - MK-8 [At baseline only]
Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
- Concentration of blood menaquinones (vitamin K2) - MK-9 [At baseline only]
Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
- Concentration of blood menaquinones (vitamin K2) - MK-10 [At baseline only]
Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
- Concentration of blood menaquinones (vitamin K2) - MK-11 [At baseline only]
Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
- Concentration of blood menaquinones (vitamin K2) - MK-12 [At baseline only]
Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
- Concentration of blood menaquinones (vitamin K2) - MK-13 [At baseline only]
Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
Secondary Outcome Measures
- Concentration of blood fetuin A [At baseline only]
Fetuin A will be quantified using enzyme-linked immunosorbent assay
- Concentration of urine fetuin A [At baseline only]
Fetuin A will be quantified using enzyme-linked immunosorbent assay
- Percentage of blood Hemoglobin A1C (HbA1c) [At baseline only]
HbA1c will be quantified in the core laboratory as per established protocols
- Total plasma calcium [At baseline only]
Calcium levels will be quantified in the core laboratory
- Concentration of ionized calcium in blood [At baseline only]
Calcium levels will be quantified in the core laboratory
- Concentration of blood albumin [At baseline only]
Albumin levels will be quantified in the core laboratory as per established protocols
- Concentration of urinary γ-carboxyglutamic acid [At baseline only]
γ-carboxyglutamic acid will be quantified using high-performance liquid chromatography and normalized to creatinine
- Concentration of urinary creatinine [At baseline only]
Creatinine will be quantified using high-performance liquid chromatography
- Concentration of urinary oxalate [At baseline only]
Oxalate will be quantified using high-performance liquid chromatography and normalized to creatinine
- Concentration of urinary phosphate [At baseline only]
Phosphate will be quantified in the core laboratory as per established protocols
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male/Female, 18 - 65 years old
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No self-reported kidney stones during their lifetime (controls)
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Ultrasound examination confirming absence of kidney stones (controls)
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Have had at least 1 incidence of a clinically confirmed calcium-based kidney stone in the last 12 months (stone formers)
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Ability to collect a clean catch urine sample
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Prescription and over-the-counter drugs unchanged for ≥30 days
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Willingness to provide medical information, blood, urine, and fecal samples
Exclusion Criteria:
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Current, or within 30 days, use of antibiotics or antifungals
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Current, or within 30 days, use of vitamin K antagonists
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Current probiotic use or any use within 14 days of screening sample collection should be recorded
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A history or currently undergoing immunosuppressive drug therapy, chemotherapy, or radiation therapy 2021-06-29 1.0 Page 4 of 6
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Fecal incontinence
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History of disorder with abnormal calcium regulation such as hyperparathyroidism, active malignancy, or osteoporosis.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Lawson Health Research Institute
- St. Joseph's Health Care London
Investigators
- Principal Investigator: Jennifer Bjazevic, MD, Lawson Heath Research
Study Documents (Full-Text)
None provided.More Information
Publications
- Fraser JD, Price PA. Lung, heart, and kidney express high levels of mRNA for the vitamin K-dependent matrix Gla protein. Implications for the possible functions of matrix Gla protein and for the tissue distribution of the gamma-carboxylase. J Biol Chem. 1988 Aug 15;263(23):11033-6.
- Moe OW. Kidney stones: pathophysiology and medical management. Lancet. 2006 Jan 28;367(9507):333-44. Review.
- Stanford J, Charlton K, Stefoska-Needham A, Ibrahim R, Lambert K. The gut microbiota profile of adults with kidney disease and kidney stones: a systematic review of the literature. BMC Nephrol. 2020 Jun 5;21(1):215. doi: 10.1186/s12882-020-01805-w.
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