Evaluating the Vitamin K2 Status of Calcium-based Stone Formers

N/ACompletedNCT05081960

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's60 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Kidney Calculi Calcium Oxalate Kidney Stones Vitamin K 2 Human Kidney Stone

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Male/Female, 18 - 65 years old * No self-reported kidney stones during their lifetime (controls) * Ultrasound examination confirming absence of kidney stones (controls) * Have had at least 1 incidence of a clinically confirmed calcium-based kidney stone in the last 12 months (stone formers) * Ability to collect a clean catch urine sample * Prescription and over-the-counter drugs unchanged for ≥30 days * Willingness to provide medical information, blood, urine, and fecal samples Exclusion Criteria: * Current, or within 30 days, use of antibiotics or antifungals * Current, or within 30 days, use of vitamin K antagonists * Current probiotic use or any use within 14 days of screening sample collection should be recorded * A history or currently undergoing immunosuppressive drug therapy, chemotherapy, or radiation therapy 2021-06-29 1.0 Page 4 of 6 * Fecal incontinence * History of disorder with abnormal calcium regulation such as hyperparathyroidism, active malignancy, or osteoporosis.

Outcomes

Primary Outcomes

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.

Time frame: At baseline only

Concentration of urine dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein)

dp-ucMGP will be quantified using an enzyme-linked immunosorbent assay

Time frame: At baseline only

Concentration of blood dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein)

dp-ucMGP will be quantified using an enzyme-linked immunosorbent assay

Time frame: At baseline only

Concentration of blood total osteocalcin (OC)

Total OC will be quantified using an enzyme-linked immunosorbent assay

Time frame: At baseline only

Concentration of blood undercarboxylated osteocalcin (ucOC)

ucOC will be quantified using an enzyme-linked immunosorbent assay

Time frame: At baseline only

Concentration of urine total osteocalcin (OC)

Total OC will be quantified using an enzyme-linked immunosorbent assay

Time frame: At baseline only

Concentration of urine undercarboxylated osteocalcin (ucOC)

ucOC will be quantified using an enzyme-linked immunosorbent assay

Time frame: At baseline only

Concentration of blood menaquinones (vitamin K2) - MK-4