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| Name | Class |
|---|---|
| St. Joseph's Health Care London | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| Fecal microbiota composition of stone-formers and controls | Fecal samples will be collected using out validated toilet paper method. Microbial DNA will be extracted and sequenced using next-generation sequencing. | At baseline only |
| Concentration of urine dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein) | dp-ucMGP will be quantified using an enzyme-linked immunosorbent assay | At baseline only |
| Concentration of blood dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein) | dp-ucMGP will be quantified using an enzyme-linked immunosorbent assay | At baseline only |
| Concentration of blood total osteocalcin (OC) | Total OC will be quantified using an enzyme-linked immunosorbent assay | At baseline only |
| Concentration of blood undercarboxylated osteocalcin (ucOC) | ucOC will be quantified using an enzyme-linked immunosorbent assay | At baseline only |
| Concentration of urine total osteocalcin (OC) | Total OC will be quantified using an enzyme-linked immunosorbent assay | At baseline only |
| Concentration of urine undercarboxylated osteocalcin (ucOC) | ucOC will be quantified using an enzyme-linked immunosorbent assay | At baseline only |
| Measure | Description | Time Frame |
|---|---|---|
| Concentration of blood fetuin A | Fetuin A will be quantified using enzyme-linked immunosorbent assay | At baseline only |
| Concentration of urine fetuin A | Fetuin A will be quantified using enzyme-linked immunosorbent assay |
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Inclusion Criteria:
Exclusion Criteria:
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Stone formers will be recruited from the Urology clinic or London and surrounding community. Controls will be recruited from the London and surrounding community.
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| Name | Affiliation | Role |
|---|---|---|
| Jennifer Bjazevic, MD | Lawson Heath Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Joseph's Health Care London | London | Ontario | N6J 3T9 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 3042764 | Background | 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. | |
| 16443041 | Background | Moe OW. Kidney stones: pathophysiology and medical management. Lancet. 2006 Jan 28;367(9507):333-44. doi: 10.1016/S0140-6736(06)68071-9. |
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Urine, fecal, and blood samples will be collected.
| Concentration of blood menaquinones (vitamin K2) - MK-4 | Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence. | At baseline only |
| Concentration of blood menaquinones (vitamin K2) - MK-7 | Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence. | At baseline only |
| Concentration of blood menaquinones (vitamin K2) - MK-8 | Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence. | At baseline only |
| Concentration of blood menaquinones (vitamin K2) - MK-9 | Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence. | At baseline only |
| Concentration of blood menaquinones (vitamin K2) - MK-10 | Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence. | At baseline only |
| Concentration of blood menaquinones (vitamin K2) - MK-11 | Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence. | At baseline only |
| Concentration of blood menaquinones (vitamin K2) - MK-12 | Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence. | At baseline only |
| Concentration of blood menaquinones (vitamin K2) - MK-13 | Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence. | At baseline only |
| At baseline only |
| Percentage of blood Hemoglobin A1C (HbA1c) | HbA1c will be quantified in the core laboratory as per established protocols | At baseline only |
| Total plasma calcium | Calcium levels will be quantified in the core laboratory | At baseline only |
| Concentration of ionized calcium in blood | Calcium levels will be quantified in the core laboratory | At baseline only |
| Concentration of blood albumin | Albumin levels will be quantified in the core laboratory as per established protocols | At baseline only |
| Concentration of urinary γ-carboxyglutamic acid | γ-carboxyglutamic acid will be quantified using high-performance liquid chromatography and normalized to creatinine | At baseline only |
| Concentration of urinary creatinine | Creatinine will be quantified using high-performance liquid chromatography | At baseline only |
| Concentration of urinary oxalate | Oxalate will be quantified using high-performance liquid chromatography and normalized to creatinine | At baseline only |
| Concentration of urinary phosphate | Phosphate will be quantified in the core laboratory as per established protocols | At baseline only |
| 32503496 | Background | 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. |
| 37161031 | Background | Chmiel JA, Stuivenberg GA, Al KF, Akouris PP, Razvi H, Burton JP, Bjazevic J. Vitamins as regulators of calcium-containing kidney stones - new perspectives on the role of the gut microbiome. Nat Rev Urol. 2023 Oct;20(10):615-637. doi: 10.1038/s41585-023-00768-5. Epub 2023 May 9. |
| 7895417 | Result | Conly J, Stein K. Reduction of vitamin K2 concentrations in human liver associated with the use of broad spectrum antimicrobials. Clin Invest Med. 1994 Dec;17(6):531-9. |
| 23140417 | Result | Sato T, Schurgers LJ, Uenishi K. Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutr J. 2012 Nov 12;11:93. doi: 10.1186/1475-2891-11-93. |
| 22498635 | Result | Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012 Jul;62(1):160-5. doi: 10.1016/j.eururo.2012.03.052. Epub 2012 Mar 31. |
| 11356998 | Result | Schurgers LJ, Vermeer C. Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis. 2000 Nov-Dec;30(6):298-307. doi: 10.1159/000054147. |
| 11960685 | Result | Schurgers LJ, Vermeer C. Differential lipoprotein transport pathways of K-vitamins in healthy subjects. Biochim Biophys Acta. 2002 Feb 15;1570(1):27-32. doi: 10.1016/s0304-4165(02)00147-2. |
| 28340119 | Result | Wei FF, Thijs L, Zhang ZY, Jacobs L, Yang WY, Salvi E, Citterio L, Cauwenberghs N, Kuznetsova T, E A Drummen N, Hara A, Manunta P, Li Y, Verhamme P, Allegaert K, Cusi D, Vermeer C, Staessen JA. The risk of nephrolithiasis is causally related to inactive matrix Gla protein, a marker of vitamin K status: a Mendelian randomization study in a Flemish population. Nephrol Dial Transplant. 2018 Mar 1;33(3):514-522. doi: 10.1093/ndt/gfx014. |
| ID | Term |
|---|---|
| D007669 | Kidney Calculi |
| C563477 | Nephrolithiasis, Calcium Oxalate |
| D053040 | Nephrolithiasis |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052878 | Urolithiasis |
| D014545 | Urinary Calculi |
| D052801 | Male Urogenital Diseases |
| D002137 | Calculi |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
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