title: Hypomagnesemia and the risk of death and GFR decline in chronic kidney disease.
abstract: BACKGROUND
  Hypomagnesemia predicts cardiovascular morbidity and mortality in the general population and accelerated loss of kidney function in renal transplant recipients and diabetics. It is associated with risk factors for cardiovascular and renal injury such as hyperaldosteronism, endothelial dysfunction, oxidative stress, insulin resistance, and hypertension. We aimed to establish the prognostic significance of hypomagnesemia for all-cause mortality and decline in estimated glomerular filtration rate (eGFR) in chronic kidney disease.
  
  
  METHODS
  Baseline parameters and serial follow-up measurements of serum creatinine were obtained in 1650 patients with chronic kidney disease and follow-up in a tertiary hospital between January 2002 and June 2011. We used Cox proportional hazards regression to assess the predictive value of magnesium for all-cause mortality and a random-effects mixed linear model for longitudinal analysis of the effect of serum magnesium on eGFR decline.
  
  
  RESULTS
  After a median follow-up of 5.1 years, 284 deaths occurred. Higher magnesium was associated with reduced mortality (adjusted hazard ratio 0.930 per 0.1 mg/dL increase; 95% confidence interval [CI], 0.887-0.974; P = .002) after adjustment for potential confounders including age, sex, diabetes, kidney function, and hypertension. Patients with low (<1.8 mg/dL) versus high (>2.2 mg/dL) serum magnesium had a 61% increased mortality risk (adjusted hazard ratio 1.613; 95% CI, 1.113-2.338; P = .012). On average, eGFR changed by 0.934 per year (95% CI, 0.927-0.941; P <.0001) or an annual decrease of 6.6%. After adjustment for age, sex, diabetes, and hypertension, this change was modified by a factor of 1.033 (95% CI, 1.003-1.065; P = .032) per 1-mg/dL increase in baseline magnesium, corresponding to an annual eGFR decrease of 3.5%. The effect of magnesium lost significance after adjustment for additional covariates, including diuretics.
  
  
  CONCLUSIONS
  Hypomagnesemia predicts mortality and kidney function decline in chronic kidney disease patients. Confounding factors and treatment effects may affect these associations. Its potential as a modifiable risk factor remains to be established.
authors.affiliation: Renal Division, Department of Internal Medicine, Ghent University Hospital, Belgium. steven.vanlaecke@ugent.be
authors.forename: Steven
authors.initials: S
authors.lastname: Van Laecke
authors.forename: Evi V
authors.initials: EV
authors.lastname: Nagler
authors.forename: Francis
authors.initials: F
authors.lastname: Verbeke
authors.forename: Wim
authors.initials: W
authors.lastname: Van Biesen
authors.forename: Raymond
authors.initials: R
authors.lastname: Vanholder
mesh_terms: D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality* / Q000503:physiopathology; D007677:Kidney Function Tests; D016014:Linear Models; D008274:Magnesium / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D003404:Creatinine; D008274:Magnesium
keywords: Chronic kidney disease; Magnesium; Mortality; Outcome