title: Iron supplementation associates with low mortality in pre-dialyzed advanced chronic kidney disease patients receiving erythropoiesis-stimulating agents: a nationwide database analysis.
abstract: BACKGROUND
  A risk/benefit analysis of iron supplementation in pre-dialysis advanced chronic kidney disease (CKD) patients has not been conducted. We aim to assess the effectiveness and the safety of iron supplementation in patients with CKD Stage 5 who have not yet received dialysis (CKD 5 ND).
  
  
  METHODS
  A prospective cohort study was conducted based on the Taiwan National Health Insurance Research Database. From 1 January 2000 to 30 June 2009, we enrolled 31 971 adult patients who had a serum creatinine >6 mg/dL and a haematocrit <28% and who were treated with erythropoiesis-stimulating agents (ESAs). All patients were further divided into two groups with or without iron supplementation within 90 days after starting ESA therapy. Patient follow-up took place until dialysis, death before initiation of dialysis or 31 December 2009. The primary outcomes were death before initiating dialysis, hospitalization before death or long-term dialysis.
  
  
  RESULTS
  After propensity score matching, the patients who received iron supplementation were associated with a lower risk of all-cause death [hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.80-0.90] compared with non-users. The survival benefit of iron use was consistent across the majority of dosage groups, except for those who were treated with monthly IV iron >200 mg. Moreover, compared with the non-users, the iron users were associated with a lower risk of hospitalizations (HR, 0.97; 95% CI, 0.94-0.99) but with a higher risk of faster progression to end-stage renal disease (HR, 1.05; 95% CI, 1.01-1.08).
  
  
  CONCLUSIONS
  Iron supplementation is associated with 15% risk reduction in death among CKD 5 ND patients who received ESA treatment. Randomized studies are needed to validate this association.
authors.affiliation: Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Ko-Lin
authors.initials: KL
authors.lastname: Kuo
authors.affiliation: Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Szu-Chun
authors.initials: SC
authors.lastname: Hung
authors.affiliation: Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Jia-Sin
authors.initials: JS
authors.lastname: Liu
authors.affiliation: Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Yu-Kang
authors.initials: YK
authors.lastname: Chang
authors.affiliation: Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan Department of Health Services Administration, China Medical University, Taichung, Taiwan.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Tarng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016208:Databases, Factual; D019587:Dietary Supplements; D018450:Disease Progression; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D006435:Renal Dialysis / Q000401:mortality*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality*; D013223:Statistics as Topic; D015996:Survival Rate; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
chemical_list: D006397:Hematinics; C066317:ferryl iron; D007501:Iron
keywords: chronic kidney disease; dialysis; erythropoiesis-stimulating agent; iron supplementation