title: Inhaled nitric oxide and the risk of renal dysfunction in patients with acute respiratory distress syndrome: a propensity-matched cohort study.
abstract: BACKGROUND
  Inhaled nitric oxide (iNO) is a rescue therapy for severe hypoxemia in patients with acute respiratory distress syndrome (ARDS). Pooled data from clinical trials have signaled a renal safety warning for iNO therapy, but the significance of these findings in daily clinical practice is unclear. We used primary data to evaluate the risk of iNO-associated renal dysfunction in patients with ARDS.
  
  
  METHODS
  We conducted a cohort study using data from a tertiary teaching hospital to evaluate the risk of incident renal replacement therapy (RRT) in iNO users compared with that of non-users. Propensity score matching and competing-risks regression were used for data analysis. Residual confounding was assessed by means of a rule-out approach. We also evaluated effect modification by pre-specified factors using stratified analysis.
  
  
  RESULTS
  We identified 547 patients with ARDS, including 216 iNO users and 331 non-users. At study entry, 313 (57.2%) patients had moderate ARDS and 234 (42.8%) had severe ARDS. The mean patient age was 63 ± 17 years. The crude hazard ratio of the need for RRT in iNO users compared with non-users was 2.23 (95% CI, 1.61-3.09, p < 0.001). After propensity score matching, there were 151 iNO users matched to 151 non-users. The adjusted hazard ratio was 1.59 (95% CI, 1.08-2.34, p = 0.02). In the stratified analysis, we found that older aged patients (≥65 years) were more susceptible to iNO-associated kidney injury than younger patients (p = 0.05).
  
  
  CONCLUSIONS
  This study showed that iNO substantially increased the risk of renal dysfunction in patients with ARDS. Older aged patients were especially susceptible to this adverse event.
authors.affiliation: Institute of Epidemiology and Preventive Medicine, National Taiwan University, No.17 Xu-Zhou Road, Taipei, 10020, Taiwan. syruan@ntu.edu.tw.|Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. syruan@ntu.edu.tw.
authors.forename: Sheng-Yuan
authors.initials: SY
authors.lastname: Ruan
authors.affiliation: Institute of Epidemiology and Preventive Medicine, National Taiwan University, No.17 Xu-Zhou Road, Taipei, 10020, Taiwan.|Division of Nephrology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hon-Yen
authors.initials: HY
authors.lastname: Wu
authors.affiliation: Institute of Epidemiology and Preventive Medicine, National Taiwan University, No.17 Xu-Zhou Road, Taipei, 10020, Taiwan.
authors.forename: Hsien-Ho
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Huey-Dong
authors.initials: HD
authors.lastname: Wu
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.affiliation: Institute of Epidemiology and Preventive Medicine, National Taiwan University, No.17 Xu-Zhou Road, Taipei, 10020, Taiwan. mslai@ntu.edu.tw.
authors.forename: Mei-Shu
authors.initials: MS
authors.lastname: Lai
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D000280:Administration, Inhalation; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000009:adverse effects*; D057216:Propensity Score; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology
chemical_list: D009569:Nitric Oxide
keywords: Acute respiratory distress syndrome; Adverse effect; Nitric oxide; Renal failure; Treatment