title: Angiotensin-converting enzyme inhibitor usage and acute kidney injury: a secondary analysis of RENAL study outcomes.
abstract: OBJECTIVE
  Acute kidney injury (AKI) is associated with increased mortality. While angiotensin-converting enzyme inhibitors (ACEI) are known to slow progression of chronic kidney disease, their role in AKI remains unclear.
  
  
  METHODS
  The Randomised Evaluation of Normal vs. Augmented Level Replacement Therapy (RENAL) study data were analysed according to ACEI use over time. The primary outcome was all-cause mortality at 90 days following randomisation. Analyses used a multivariate Cox model adjusted for either baseline or for time-dependent covariates, and a sensitivity analysis of patients surviving to at least the median time to ACEI initiation.
  
  
  RESULTS
  Of the 1463 participants with available data on ACE inhibitors usage, 142 (9.7%) received ACEI at least once during study data collection. Participants treated with ACEI were older (P = 0.02) and had less sepsis at baseline (P < 0.001). ACEI use was significantly associated with lower mortality at 90 days (HR 0.46, 95% CI 0.30-0.71, P < 0.001), and an increase in renal replacement therapy-free days (P < 0.001), intensive care unit-free days (P < 0.001) and hospital free-days (P < 0.001) after adjusting for baseline covariates. Using the time-dependent analysis, however, the effect of ACEI administration was not significant (HR 0.78, 95% CI 0.51-1.21, P = 0.3). The sensitivity analysis in day 8 survivors produced similar results.
  
  
  CONCLUSIONS
  In the RENAL study cohort, the use of ACEI during the study was not common and, after adjustment for time-dependent covariates, was not significantly associated with reductions in mortality. Further assessment of the effect of ACEI use in AKI patients is needed.
authors.affiliation: Renal and Metabolic Division, The George Institute for Global Health, Sydney, New South Wales, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Amanda Y
authors.initials: AY
authors.lastname: Wang
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ninomiya
authors.forename: Serigne
authors.initials: S
authors.lastname: Lo
authors.forename: Alan
authors.initials: A
authors.lastname: Cass
authors.forename: Meg
authors.initials: M
authors.lastname: Jardine
authors.forename: Martin
authors.initials: M
authors.lastname: Gallagher
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001315:Australia; D016009:Chi-Square Distribution; D005260:Female; D017583:Hemodiafiltration / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: acute kidney injury; angiotensin-converting enzyme inhibitor; dialysis; mortality; prospective study