A Randomized Trial of Magnesium Oxide and Oral Carbon Adsorbent for Coronary Artery Calcification in Predialysis CKD - PubMed (original) (raw)

Randomized Controlled Trial

. 2019 Jun;30(6):1073-1085.

doi: 10.1681/ASN.2018111150. Epub 2019 Apr 29.

Takayuki Hamano 2, Yoshitsugu Obi 3, Chikako Monden 4, Tatsufumi Oka 5, Satoshi Yamaguchi 5, Isao Matsui 5, Nobuhiro Hashimoto 5, Ayumi Matsumoto 5, Karin Shimada 5, Yoshitsugu Takabatake 5, Atsushi Takahashi 5, Jun-Ya Kaimori 6, Toshiki Moriyama 7, Ryohei Yamamoto 7, Masaru Horio 8, Koichi Yamamoto 9, Ken Sugimoto 9, Hiromi Rakugi 9, Yoshitaka Isaka 5

Affiliations

Randomized Controlled Trial

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

Yusuke Sakaguchi et al. J Am Soc Nephrol. 2019 Jun.

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.

Copyright © 2019 by the American Society of Nephrology.

PubMed Disclaimer

Figures

Figure 1.

Figure 1.

A total of 123 patients underwent randomization. (A) Flow chart of the first 125 enrolled patients. (B) The numbers of patients randomized to each group (2×2 factorial design). The numbers in parentheses denote the numbers of patients who completed the study.

Figure 2.

Figure 2.

MgO, but not AST-120, retards the progression of CAC. (A) Total patients (_n_=96). (B) Patients with baseline CAC score <400 (_n_=56). (C) Patients with baseline CAC score ≥400 (_n_=40). Percentage changes in CAC scores are compared between groups using the Wilcoxon rank sum test. Data are on the basis of the full analysis set population. CACS, coronary artery calcification score; MgO, magnesium oxide.

Figure 3.

Figure 3.

MgO reduces the proportion of rapid progressors. Rapid progressors are defined as those patients with an annualized percentage change in CAC scores of ≥15%. (A) Total patients (_n_=96). (B) Patients with baseline CAC score <400 (_n_=56). (C) Patients with baseline CAC score ≥400 (_n_=40). Proportions between groups are compared using chi-squared test. Data are on the basis of the full analysis set population. CACS, coronary artery calcification score; MgO, magnesium oxide.

Figure 4.

Figure 4.

Neither MgO nor AST-120 suppresses the progression of thoracic aorta calcification. (A) Percentage changes in thoracic aorta calcification are not significantly different between the MgO group (_n_=46) and control group (_n_=50). (B) Percentage changes in thoracic aorta calcification are not significantly different between the AST-120 group (_n_=55) and control group (_n_=41). Data are on the basis of the full analysis set population. MgO, magnesium oxide.

References

    1. Braun J, Oldendorf M, Moshage W, Heidler R, Zeitler E, Luft FC: Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients. Am J Kidney Dis 27: 394–401, 1996 - PubMed
    1. Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, et al.: Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 342: 1478–1483, 2000 - PubMed
    1. Fox CS, Larson MG, Keyes MJ, Levy D, Clouse ME, Culleton B, et al.: Kidney function is inversely associated with coronary artery calcification in men and women free of cardiovascular disease: The Framingham Heart Study. Kidney Int 66: 2017–2021, 2004 - PubMed
    1. Russo D, Corrao S, Miranda I, Ruocco C, Manzi S, Elefante R, et al.: Progression of coronary artery calcification in predialysis patients. Am J Nephrol 27: 152–158, 2007 - PubMed
    1. Kramer H, Toto R, Peshock R, Cooper R, Victor R: Association between chronic kidney disease and coronary artery calcification: The Dallas Heart Study. J Am Soc Nephrol 16: 507–513, 2005 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources