A Randomized Trial of Magnesium Oxide and Oral Carbon Adsorbent for Coronary Artery Calcification in Predialysis CKD

J Am Soc Nephrol. 2019 Jun;30(6):1073-1085. doi: 10.1681/ASN.2018111150. Epub 2019 Apr 29.

Abstract

Background: Developing strategies for managing coronary artery calcification (CAC) in patients with CKD is an important clinical challenge. Experimental studies have demonstrated that magnesium inhibits vascular calcification, whereas the uremic toxin indoxyl sulfate aggravates it.

Methods: To assess the efficacy of magnesium oxide (MgO) and/or the oral carbon adsorbent AST-120 for slowing CAC progression in CKD, we conducted a 2-year, open-label, randomized, controlled trial, enrolling patients with stage 3-4 CKD with risk factors for CAC (diabetes mellitus, history of cardiovascular disease, high LDL cholesterol, or smoking). Using a two-by-two factorial design, we randomly assigned patients to an MgO group or a control group, and to an AST-120 group or a control group. The primary outcome was percentage change in CAC score.

Results: We terminated the study prematurely after an interim analysis with the first 125 enrolled patients (of whom 96 completed the study) showed that the median change in CAC score was significantly smaller for MgO versus control (11.3% versus 39.5%). The proportion of patients with an annualized percentage change in CAC score of ≥15% was also significantly lower for MgO compared with control (23.9% versus 62.0%). However, MgO did not suppress the progression of thoracic aorta calcification. The MgO group's dropout rate was higher than that of the control group (27% versus 17%), primarily due to diarrhea. The percentage change in CAC score did not differ significantly between the AST-120 and control groups.

Conclusions: MgO, but not AST-120, appears to be effective in slowing CAC progression. Larger-scale trials are warranted to confirm these findings.

Keywords: chronic kidney disease; coronary artery calcification; magnesium oxide; oral carbon adsorbent; randomized controlled trial.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Carbon / administration & dosage*
  • Comorbidity
  • Coronary Artery Disease / diagnosis*
  • Coronary Artery Disease / epidemiology*
  • Coronary Artery Disease / prevention & control
  • Disease Progression
  • Female
  • Hospitals, University
  • Humans
  • Magnesium Oxide / administration & dosage*
  • Male
  • Middle Aged
  • Oxides / administration & dosage*
  • Patient Compliance / statistics & numerical data
  • Primary Prevention
  • Prognosis
  • Reference Values
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / epidemiology
  • Renal Insufficiency, Chronic / therapy
  • Severity of Illness Index
  • Treatment Outcome
  • Vascular Calcification / drug therapy*
  • Vascular Calcification / epidemiology*
  • Vascular Calcification / prevention & control

Substances

  • Oxides
  • Magnesium Oxide
  • Carbon
  • AST 120