Magnesium in chronic haemodialysis (MAGIC-HD): a study protocol for a randomised controlled trial to determine feasibility and safety of using increased dialysate magnesium concentrations to increase plasma magnesium concentrations in people treated with haemodialysis

Abstract

IntroductionPeople treated with haemodialysis are at increased risk for all-cause and cardiovascular mortality. Plasma magnesium concentration has been inversely associated with these risks. Therefore, plasma magnesium may be a new modifiable risk factor and an increase of dialysate magnesium concentration may be an easy, safe and effective way to increase plasma magnesium concentrations. Detailed information on modulating dialysate magnesium concentrations is limited in literature. Primary objective of this study is to determine the safety and feasibility to increase plasma magnesium concentrations in people treated with haemodialysis by means of sequentially increasing concentration of magnesium in the dialysate.Methods and analysisIn this randomised double-blinded standard of care controlled trial, 53 persons treated with haemodialysis will be randomly allocated 2:1 to either a stepwise individually titrated increase of dialysate magnesium concentration from 0.50 to 0.75 to 1.00 mmol/L during 8 weeks, or a standard dialysate magnesium concentration of 0.50 mmol/L. Other study measurements include dietary records, questionnaires, ECG, Holter registration and pulse wave velocity. The primary endpoint is predialysis plasma magnesium after the long interdialytic interval at the end of week 8. In addition, the predictive effect of dialysate magnesium concentration and other baseline parameters and dialysis characteristics on plasma magnesium concentration will be explored using linear mixed models. Safety endpoint is defined by the occurrence of hypermagnesemia above 1.25 mmol/L, or bradycardia or prolonged QTc interval detected on the ECG.Ethics and disseminationThe study is conducted in accordance with the declaration of Helsinki as revised in 2013 and was approved by the Ethical Committee of the VU University Medical Centre. The results of the study will be disseminated by publication in peer-reviewed scientific journals and presentation at national or international conferences in the field of interest.Trial registration numberNTR6568/NL6393.

Magnesium Administration in Chronic Kidney Disease

“…A recent Japanese, two-year observational study in hemodialysis patients demonstrated an inverse association for Mg concentration and the risk of hip fractures, with an OR 0.96 [0.94–0.99] per 0.1 mmol/L increase of plasma Mg [ 104 ]. Although, theoretically, an extreme increase of dialysate Mg is imaginable, only cautious dialysate increases are investigated due to the risk of fast intra- and extracellular electrolyte shifts during as well as between dialysis sessions [ 44 , 46 , 99 , 105 ]. Symptomatic hypermagnesemia, generally only seen in people with serum Mg concentrations of 1.6 to 2.0 mmol/L or above, is very rare, usually iatrogenic, and can follow decreased renal excretion, intra- to extracellular compartment shifts, and most frequently from excessive intake [ 106 ].…”

“…Additionally, results of RCTs investigating the effect of increasing dialysate Mg concentration are expected. The MAGIC-HD study, is a randomized, placebo-controlled feasibility study in a hemodialysis population, with a stepwise increase of dialysate Mg from the regular 0.50 mmol/L up to 1.00 mmol/L and explorative endpoints including PWV, 48 h cardiac rhythm registrations, and several markers of vascular calcification and MBD [ 105 ]. Another large, cluster randomized clinical trial will investigate cardiovascular-related hospitalization, mortality, and patient-reported muscle cramps comparing higher (0.75 mmol/L) versus lower (0.50 mmol/L) hemodialysate Mg concentration (ClinicalTrials identifier: NCT04079582).…”