Diurnal Variation in Markers of Mineral and Bone Disease in Chronic Kidney Disease
- Conditions
- Chronic Kidney DiseasesMineral Metabolism Disorder
- Interventions
- Diagnostic Test: Blood and urine samples
- Registration Number
- NCT03698422
- Lead Sponsor
- Herlev Hospital
- Brief Summary
The purpose of this study is to examine whether there are diurnal variations in magnesium and other markers related to mineral metabolism in blood from patients with chronic kidney disease (CKD) compared to healthy controls.
- Detailed Description
CKD is associated with a mortality rate 5-10 times higher than in the general population, which is driven by a high rate of cardiovascular disease. Several cohort studies have revealed an association between hypomagnesaemia and increased mortality in patients with CKD as well as faster progression of CKD. Additionally, studies in cultured vascular smooth muscle cells (VSMC) and in rodents with CKD have shown that Mg inhibits vascular calcification.
The exact mechanism behind the inhibitory effect of Mg on vascular calcification is incompletely understood, but seems to be related to an inhibitory effect on the formation and precipitation of hydroxyapatite and delayed formation of secondary calciprotein particles, both of which have been shown to induce calcification of VSMC in vitro. Mg blocks the calcium (Ca) influx across the cell membrane in the VSMC. Mg has some affinity for the Ca sensing receptor, which has been shown to be involved in the calcification of VSMC, and might thus inhibit vascular calcification in a manner similar to other calcimimetics.
Thus, increasing serum Mg has been proposed as a possible treatment to prevent vascular calcification in CKD. However, any diurnal variation in serum Mg and other markers of mineral metabolism related to vascular calcification in CKD have not previously been described. This is relevant as monitoring of treatment with Mg supplementation might potentially be dangerous, if there are significant diurnal changes in serum Mg. Therefore, we wish to conduct a prospective controlled clinical trial to investigate any diurnal changes in Mg other markers of mineral metabolism in healthy controls, patients with predialysis CKD and patients with end-stage kidney disease (ESKD).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 22
- Age ≥ 18 years.
- Serum Mg between 0.7 and 1.1 mmol/L on average of previous measurements over the last 6 months.
- Serum ionised Ca between 1.10 and 1.35 mmol/L on average of previous measurements over the last 6 months.
- Serum phosphate (PO4) between 0.7 and 1.8 mmol/L on average of previous measurements over the last 6 months.
- A negative pregnancy test for women of childbearing age.
- Written informed consent.
- For healthy controls - estimated glomerular filtration rate (eGFR) > 60 mL/min for > 3 months and no known current or chronic medical or surgical conditions.
- For predialysis CKD subjects - estimated glomerular filtration rate (eGFR) between 30 and 15 mL/min for > 3 months (i.e. CKD stage 4).
- For ESKD subjects - maintenance haemodialysis treatment for > 3 months for ESKD and with anuria (urine excretion < 100 mL/day).
- Diagnosis of diabetes mellitus.
- Kidney transplant recipient.
- Parathyroid hormone (PTH) > 66 ρmol/L during the previous 3 months.
- Previous parathyroidectomy.
- Current treatment with Mg containing medication or supplements.
- Current treatment with calcimimetics.
- Current treatment with immunosuppressive drugs.
- Active malignant disease.
- Blood haemoglobin < 6.0 mmol/L
- Any condition impairing Mg absorption from the gastrointestinal tract (e.g. short bowel syndrome, chronic pancreatitis).
- Other diseases or conditions, which, in the opinion of the site investigator, would prevent participation in or completion of trial.
- Pregnancy or breastfeeding.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Healthy controls Blood and urine samples Estimated glomerular filtration rate (eGFR) \> 60 mL/min for \> 3 months and no known current or chronic medical or surgical conditions. Blood and urine samples are collected for every 3rd hour during 24 hours Predialysis CKD subjects Blood and urine samples Estimated glomerular filtration rate (eGFR) between 30 and 15 mL/min for \> 3 months (i.e. CKD stage 4). Blood and urine samples are collected for every 3rd hour during 24 hours ESKD subjects Blood and urine samples Maintenance haemodialysis treatment for \> 3 months for ESKD and with anuria (urine excretion \< 100 mL/day). Blood and urine samples are collected for every 3rd hour during 24 hours
- Primary Outcome Measures
Name Time Method Diurnal change in serum magnesium within groups 24 hours change in serum magnesium (mmol/l) within Groups The changes within groups over several timepoints will be compared with linear mixed effect models
- Secondary Outcome Measures
Name Time Method Change in p-FGF23 24 hours Change in p-FGF23 within and between groups
Change in u-magnesium 24 hours Change in u-magnesium within and between groups
Change in s-calcification propensity score 24 hours Change in s-calcification propensity score within and between groups
Change in serum magnesium between groups 24 hours Change in serum magnesium (mmol/l) between Groups The overall magnesium levels will be compared between groups by comparing the total mean of measurements for each group.
Change in ionized calcium 24 hours Change in p-ionized calcium within and between groups
Change in p-phosphate 24 hours Change in p-phosphate within and between groups
Change in p-PTH 24 hours Change in p-PTH within and between groups
Trial Locations
- Locations (1)
Herlev Hospital
🇩🇰Herlev, Denmark