Legal Performance-enhancing Drugs Alter Course and Treatment of Rhabdomyolysis-induced Acute Kidney Injury.

Autor: Hebert JF; Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR 97239, USA., Eiwaz MB; Operative Care Division, Portland Veterans Administration Medical Center, Portland, OR 97239, USA., Nickerson MN; Operative Care Division, Portland Veterans Administration Medical Center, Portland, OR 97239, USA., Munhall AC; Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR 97239, USA., Pai AA; Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR 97239, USA., Groat T; Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR 97239, USA., Andeen NK; Department of Pathology, Oregon Health and Science University, Portland, OR 97239, USA., Hutchens MP; Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR 97239, USA.; Operative Care Division, Portland Veterans Administration Medical Center, Portland, OR 97239, USA.
Jazyk: angličtina
Zdroj: Military medicine [Mil Med] 2023 Nov 08; Vol. 188 (Suppl 6), pp. 346-353.
DOI: 10.1093/milmed/usad142
Abstrakt: Introduction: Rhabdomyolysis-induced acute kidney injury (RIAKI) can interrupt physical training and increase mortality in injured warfighters. The legal performance-enhancing drugs caffeine and ibuprofen, which can cause renal injury, are widely used by service members. Whether caffeine or ibuprofen affects RIAKI is unknown. Cilastatin treatment was recently identified as an experimental treatment to prevent RIAKI at injury. To determine potential interacting factors in RIAKI treatment, we test the hypothesis that caffeine and ibuprofen worsen RIAKI and interfere with treatment.
Materials and Methods: In mice, RIAKI was induced by glycerol intramuscular injection. Simultaneously, mice received caffeine (3 mg/kg), ibuprofen (10 mg/kg), or vehicle. A second cohort received volume resuscitation (PlasmaLyte, 20 mL/kg) in addition to caffeine or ibuprofen. In a third cohort, cilastatin (200 mg/kg) was administered concurrently with drug and glycerol administration. Glomerular filtration rate (GFR), blood urea nitrogen (BUN), urine output (UOP), renal pathology, and renal immunofluorescence for kidney injury molecule 1 were quantified after 24 hours.
Results: Caffeine did not worsen RIAKI; although BUN was modestly increased by caffeine administration, 24-hour GFR, UOP, and renal histopathology were similar between vehicle-treated, caffeine-treated, and caffeine + PlasmaLyte-treated mice. Ibuprofen administration greatly worsened RIAKI (GFR 14.3 ± 19.5 vs. 577.4 ± 454.6 µL/min/100 g in control, UOP 0.5 ± 0.4 in ibuprofen-treated mice vs. 2.7 ± 1.7 mL/24 h in control, and BUN 264 ± 201 in ibuprofen-treated mice vs. 66 ± 21 mg/dL in control, P < .05 for all); PlasmaLyte treatment did not reverse this effect. Cilastatin with or without PlasmaLyte did not reverse the deleterious effect of ibuprofen in RIAKI.
Conclusions: Caffeine does not worsen RIAKI. The widely used performance-enhancing drug ibuprofen greatly worsens RIAKI in mice. Standard or experimental treatment of RIAKI including the addition of cilastatin to standard resuscitation is ineffective in mice with RIAKI exacerbated by ibuprofen. These findings may have clinical implications for the current therapy of RIAKI and for translational studies of novel treatment.
(Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)
Databáze: MEDLINE
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