title: Effect of spironolactone on the risks of mortality and hospitalization for heart failure in pre-dialysis advanced chronic kidney disease: A nationwide population-based study.
abstract: BACKGROUND
  Spironolactone has been shown to reduce cardiovascular death in patients with mild-to-moderate chronic kidney disease (CKD), but its risks and benefits in advanced CKD remain unsettled. We aimed to assess whether spironolactone reduces cardiovascular mortality and morbidity in pre-dialysis stage 5 CKD patients.
  
  
  METHODS
  Using Taiwan's National Health Insurance Research Database from January 2000 to June 2009, we enrolled 27,213 pre-dialysis stage 5 CKD adult patients, in whom 1363 patients were treated with spironolactone (user) and 25,850 were not (nonuser). Outcomes were all-cause mortality, hospitalization for heart failure (HHF) and major adverse cardiac event (MACE, the composite of acute myocardial infarction and ischemic stroke). Patients were followed up till December 31, 2009.
  
  
  RESULTS
  Over 85,758 person-years of follow-up, spironolactone users had higher incidence for all-cause mortality (24.7/100 person-years vs. 10.6/100 person-years), infection-related death (4.4/100 person-years vs. 1.7/100 person-years) and HHF (4.0/100 person-years vs. 1.4/100 person-years). Multivariable Cox hazards model showed that spironolactone users were associated with higher risks of all-cause mortality (adjusted hazard ratio [aHR] 1.35, 95% confidence interval [CI] 1.24-1.46), infection-related death (aHR 1.42, CI 1.16-1.73) and HHF (aHR 1.35, CI 1.08-1.67) as compared to nonusers. The risks for cardiovascular mortality, MACE and hyperkalemia-associated hospitalization were similar between two groups. After matching users and nonusers (1:3 ratio) by propensity scores, the results were consistent in matched cohort and across subgroups.
  
  
  CONCLUSIONS
  Spironolactone may be associated with higher risks for all-cause and infection-related mortality and HHF in pre-dialysis stage 5 CKD patients. Spironolactone should be used with caution in advanced CKD patients.
authors.affiliation: Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Tseng
authors.affiliation: Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Jia-Sin
authors.initials: JS
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taipei, Taiwan.
authors.forename: Szu-Chun
authors.initials: SC
authors.lastname: Hung
authors.affiliation: Division of Nephrology, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taipei, Taiwan.
authors.forename: Ko-Lin
authors.initials: KL
authors.lastname: Kuo
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yu-Hsin
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: dctarng@vghtpe.gov.tw.
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Tarng
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan; Department of Health Services Administration, China Medical University, Taichung, Taiwan. Electronic address: cch@nhri.org.tw.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Hsu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000139:chemically induced / Q000401:mortality*; D006760:Hospitalization / Q000639:trends*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D011159:Population Surveillance / Q000379:methods; D006435:Renal Dialysis / Q000401:mortality / Q000639:trends; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000401:mortality*; D013148:Spironolactone / Q000009:adverse effects / Q000627:therapeutic use*; D013624:Taiwan / Q000453:epidemiology
chemical_list: D004232:Diuretics; D013148:Spironolactone
keywords: Advanced chronic kidney disease; Heart failure; Mortality; Spironolactone