The Effect of Increasing Dialysate Magnesium on Calcification Propensity in Subjects on Haemodialysis

Study Overview
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Brief Summary
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The purpose of this trial is to examine the effect of increasing dialyse magnesium on serum calcification propensity in subjects with end-stage renal disease treated with haemodialysis.

Detailed Description
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Patients with end-stage renal disease (ESRD) have a 20-fold increased risk of cardiovascular mortality compared to the general population. Arterial stiffness, likely due to vascular calcification (VC), has been shown to predict cardiovascular mortality in ESRD. Serum calcification propensity (T50) is a novel biomarker, which is believed to reflect the propensity toward ectopic calcification (e.g. VC). Increasing serum magnesium (sMg) should increase T50, which might in turn reduce the formation of VC in patients with ESRD. A cheap and easy way of achieving this would be to increase the concentration of Mg in the dialysate (dMg) of patients with ESRD treated with haemodialysis (HD). The investigators wish to conduct a randomised controlled double-blind clinical trial to examine whether increasing dMg will improve T50 in subjects with ESRD treated with HD.

Official Title
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The Effect of Increasing Dialysate Magnesium on Serum Calcification Propensity in Subjects With End-Stage Renal Disease Treated With Haemodialysis - A Randomised Clinical Trial

Conditions
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Endstage Renal Disease

Intervention / Treatment
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* Other: Dialysate magnesium (1.0 mmol/L)
* Other: Dialysate magnesium (0.5 mmol/L)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. Treatment with maintenance haemodialysis for more than 3 months. Dialysate magnesium of 0.5 mmol/L (standard concentration). Serum magnesium < 1.2 mmol/L on average of previous measurements within the last 3 months. Women of childbearing age must be actively using contraceptive therapy (p-pills, estrogen depots or intrauterine device) as well as have a negative pregnancy test. Written informed consent. Exclusion Criteria: Treatment with peritoneal dialysis. Parathyroid hormone > 66 ρmol/L. Previous parathyroidectomy. Current treatment with magnesium containing medication or supplements. Other diseases or conditions, which, in the opinion of the site investigator, would prevent participation in or completion of the trial. Pregnancy or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dialysate magnesium 1.0 mmol/L<br>Increase dialysate magnesium from 0.5 mmol/L to 1.0 mmol/L. | Other: Dialysate magnesium (1.0 mmol/L)<br>* Dialysate magnesium will be increased from 0.5 mmol/L to 1.0 mmol/L for 4 weeks after which subjects will return to dialysate magnesium 0.5 mmol/L for 2 weeks observation.<br>|
| Active Comparator: Dialysate magnesium 0.5 mmol/L<br>Maintain dialysate magnesium at 0.5 mmol/L. | Other: Dialysate magnesium (0.5 mmol/L)<br>* Dialysate magnesium will be maintained at 0.5 mmol/L for the duration of the trial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between-group difference in serum calcification propensity at follow-up |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Within-group change in serum calcification propensity |  | 2 weeks | 
| Within-group change and between-group difference in serum magnesium |  | 4 weeks | 
| Change in serum magnesium after intervention |  | 2 weeks | 
| Within-group change and between-group difference in serum parathyroid hormone |  | 4 weeks | 
| Change in serum parathyroid hormone after intervention |  | 2 weeks | 
| Change in fibroblast growth factor 23 during intervention |  | 4 weeks | 
| Incidence of intradialytic hypotension during intervention |  | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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magnesium, ectopic calcification, chronic kidney disease - mineral and bone disorder, serum calcification propensity