Silbert Benjamin I, Ho Kwok M, Lipman Jeffrey, Roberts Jason A, Corcoran Tomas B, Morgan David J, Pavey Warren, Mas Emilie, Barden Anne E, Mori Trevor A
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 .
Antioxid Redox Signal. 2017 Feb 10;26(5):221-226. doi: 10.1089/ars.2016.6845. Epub 2016 Sep 15.
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 F-isoprostanes (F-IsoPs), markers of in vivo oxidative stress, in plasma and urine following intravenous furosemide. Urine F-IsoPs were higher in sepsis (p = 0.001) and increased in proportion to urine furosemide (p = 0.001). The furosemide-induced increase in urine F-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 F-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.
速尿是一种袢利尿剂，用于增加急性肾损伤（AKI）患者的尿量。速尿在AKI中的益处是否超过其潜在危害仍不确定。我们通过测量静脉注射速尿后血浆和尿液中F-异前列腺素（F-IsoPs，体内氧化应激标志物）的变化，研究速尿是否会影响30例AKI危重症患者的氧化应激。脓毒症患者的尿F-IsoPs较高（p = 0.001），且与尿速尿成比例增加（p = 0.001）。速尿引起的尿F-IsoPs增加因AKI严重程度而异（p < 0.001），在AKI最严重的患者中增加最大。速尿对血浆F-IsoPs无影响。我们首次证明速尿会增加AKI患者的肾脏氧化应激，并发现可能接受最大剂量速尿的AKI最严重患者的氧化应激增加最大。这些发现引发了一个假设，即给少尿型AKI患者使用大剂量速尿以使其转变为非少尿型AKI的常见做法可能会在肾脏中诱发有害的氧化应激，因此需要进行一项足够有力的随机对照试验来确定这种给药策略的临床益处是否能证明其潜在危害是合理的。《抗氧化与氧化还原信号》26卷，221 - 226页。
