title: Does Furosemide Increase Oxidative Stress in Acute Kidney Injury?
abstract: Furosemide, a loop diuretic, is used to increase urine output in patients with acute kidney injury (AKI). It remains uncertain whether the benefits of furosemide in AKI outweigh its potential harms. We investigated if furosemide influenced oxidative stress in 30 critically ill patients with AKI by measuring changes in F2-isoprostanes (F2-IsoPs), markers of in vivo oxidative stress, in plasma and urine following intravenous furosemide. Urine F2-IsoPs were higher in sepsis (p = 0.001) and increased in proportion to urine furosemide (p = 0.001). The furosemide-induced increase in urine F2-IsoPs differed depending on AKI severity (p < 0.001) and was greatest in those with the most severe AKI. Furosemide had no effect on plasma F2-IsoPs. We demonstrate for the first time that furosemide increases renal oxidative stress in AKI and find that patients with the most severe AKI-to whom the largest doses are likely to be administered-showed the greatest increase in oxidative stress. These findings lead to the hypothesis that the common practice of administering high-dose furosemide to convert oliguric to nonoliguric AKI may induce harmful oxidative stress in the kidneys, and an adequately powered, randomized controlled trial is required to determine if clinical benefits of this dosing strategy justify its potential harms. Antioxid. Redox Signal. 26, 221-226.
authors.affiliation: 1 Department of Intensive Care Medicine, Fiona Stanley Hospital , Murdoch, Australia .|2 School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia , Perth, Australia .
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Silbert
authors.affiliation: 3 Department of Intensive Care Medicine, Royal Perth Hospital , Perth, Australia .|4 School of Population Health, University of Western Australia , Crawley, Australia .|5 School of Veterinary and Life Sciences, Murdoch University , Murdoch, Australia .
authors.forename: Kwok M
authors.initials: KM
authors.lastname: Ho
authors.affiliation: 6 Burns, Trauma and Critical Care Research Centre, School of Medicine, University of Queensland , Brisbane, Australia .|7 Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital , Herston, Australia .|8 Faculty of Health, Queensland University of Technology , Brisbane, Australia .
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: 6 Burns, Trauma and Critical Care Research Centre, School of Medicine, University of Queensland , Brisbane, Australia .|7 Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital , Herston, Australia .
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: 2 School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia , Perth, Australia .|9 Department of Anaesthesia and Pain Medicine, Royal Perth Hospital , Perth, Australia .
authors.forename: Tomas B
authors.initials: TB
authors.lastname: Corcoran
authors.affiliation: 1 Department of Intensive Care Medicine, Fiona Stanley Hospital , Murdoch, Australia .
authors.forename: David J
authors.initials: DJ
authors.lastname: Morgan
authors.affiliation: 5 School of Veterinary and Life Sciences, Murdoch University , Murdoch, Australia .|10 Department of Anaesthesia and Pain Medicine, Fiona Stanley Hospital , Murdoch, Australia .
authors.forename: Warren
authors.initials: W
authors.lastname: Pavey
authors.affiliation: 2 School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia , Perth, Australia .
authors.forename: Emilie
authors.initials: E
authors.lastname: Mas
authors.affiliation: 2 School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia , Perth, Australia .
authors.forename: Anne E
authors.initials: AE
authors.lastname: Barden
authors.affiliation: 2 School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia , Perth, Australia .
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D000368:Aged; D015415:Biomarkers; D004232:Diuretics / Q000494:pharmacology*; D028441:F2-Isoprostanes / Q000378:metabolism; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D015415:Biomarkers; D004232:Diuretics; D028441:F2-Isoprostanes; D005665:Furosemide
keywords: acute renal failure; diuretic; harms; oliguria; prevention; urine output