title: Magnesium modifies the cardiovascular mortality risk associated with hyperphosphatemia in patients undergoing hemodialysis: a cohort study.
abstract: BACKGROUND
  In vitro studies have shown inhibitory effects of magnesium (Mg) on phosphate-induced calcification of vascular smooth muscle cells, raising the possibility that maintaining a high Mg level may be useful for reducing cardiovascular risks of patients with hyperphosphatemia. We examined how serum Mg levels affect the association between serum phosphate levels and the risk of cardiovascular mortality in patients undergoing hemodialysis.
  
  
  METHODS
  A nationwide register-based cohort study was conducted using database of the Renal Data Registry of the Japanese Society for Dialysis Therapy in 2009. We identified 142,069 patients receiving in-center hemodialysis whose baseline serum Mg and phosphate levels were available. Study outcomes were one-year cardiovascular and all-cause mortality. Serum Mg levels were categorized into three groups (lower, <2.7 mg/dL; intermediate, ≥2.7, <3.1 mg/dL; and higher, ≥3.1 mg/dL).
  
  
  RESULTS
  During follow-up, 11,401 deaths occurred, out of which 4,751 (41.7%) were ascribed to cardiovascular disease. In multivariable analyses, an increase in serum phosphate levels elevated the risk of cardiovascular mortality in the lower- and intermediate-Mg groups, whereas no significant risk increment was observed in the higher-Mg group. Moreover, among patients with serum phosphate levels of ≥6.0 mg/dL, the cardiovascular mortality risk significantly decreased with increasing serum Mg levels (adjusted odds ratios [95% confidence intervals] of the lower-, intermediate-, and higher-Mg groups were 1.00 (reference), 0.81 [0.66-0.99], and 0.74 [0.56-0.97], respectively.). An interaction between Mg and phosphate on the risk of cardiovascular mortality was statistically significant (P = 0.03).
  
  
  CONCLUSIONS
  Serum Mg levels significantly modified the mortality risk associated with hyperphosphatemia in patients undergoing hemodialysis.
authors.affiliation: Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sakaguchi
authors.affiliation: Committee of Renal Data Registry, Japanese Society for Dialysis Therapy, Tokyo, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Fujii
authors.affiliation: Department of Kidney Disease and Hypertension, Osaka General Medical Center, 3-1-56 Bandaihigashi Sumiyoshi-ku, Osaka, 558-8558, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shoji
authors.affiliation: Department of Kidney Disease and Hypertension, Osaka General Medical Center, 3-1-56 Bandaihigashi Sumiyoshi-ku, Osaka, 558-8558, Japan.
authors.forename: Terumasa
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.affiliation: Committee of Renal Data Registry, Japanese Society for Dialysis Therapy, Tokyo, Japan.
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Iseki
authors.affiliation: Committee of Renal Data Registry, Japanese Society for Dialysis Therapy, Tokyo, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Tsubakihara
authors.affiliation: Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood / Q000150:complications* / Q000401:mortality*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D054559:Hyperphosphatemia / Q000097:blood / Q000150:complications* / Q000401:mortality*; D008274:Magnesium / Q000097:blood*; D008297:Male; D016017:Odds Ratio; D010710:Phosphates / Q000097:blood; D006435:Renal Dialysis / Q000401:mortality*; D012307:Risk Factors
chemical_list: D010710:Phosphates; D008274:Magnesium