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CompletedNCT07094165Updated Jul 30, 2025

The Effects of Dexmedetomidine and Remifentanil on Kidney Injury After Muscle Compression Injury in Rats

An interventional study of Dexmedetomidine and Remifentanil in Acute Kidney Injury, Crush Injury and Rhabdomyolysis, sponsored by Ankara City Hospital Bilkent. Completed at 1 site in Turkey (Türkiye). Per ClinicalTrials.gov, last updated 2025-07-30.

Sponsored by Ankara City Hospital Bilkent · Not applicable, Interventional, and Basic science

From the registry’s dates

  • Registered 1 year after the study started (first participant enrolled Jul 2024, registered Jul 2025).
Phase
Not applicable
Study type
Interventional
Enrollment
28
Allocation
Randomized
Sex
All
01

Study summary

The goal of this interventional preclinical study is to evaluate the potential protective effects of two intravenous anesthetic agents-dexmedetomidine and remifentanil-on kidney function in the context of muscle crush injury, which is known to be a major contributor to acute kidney injury (AKI) following trauma, entrapment, or disasters such as earthquakes. AKI following crush syndrome results from rhabdomyolysis, hypovolemia, oxidative stress, and systemic inflammation, and it significantly increases morbidity and mortality. This study explores whether anesthetic choice during the acute phase of injury influences renal outcomes.

This study used a rat model of crush injury. A total of 28 healthy adult male Wistar rats were randomly divided into four groups (n=7 per group):

  1. Control group - no surgical procedure, no injury, no drug.
  2. Sham group - anesthesia and cannulation were performed but no crush injury or drug administered.
  3. Dexmedetomidine group - crush injury + intravenous dexmedetomidine infusion (3 µg/kg/h) for 1 hour.
  4. Remifentanil group - crush injury + intravenous remifentanil infusion (1 µg/kg/h) for 1 hour.

Crush injury was induced by applying a metal clamp with a constant pressure of 3 kg to both gastrocnemius muscles for 2 hours, under anesthesia. After the clamp was removed, animals in the two treatment groups received a one-hour intravenous infusion of their assigned drug. Blood samples were taken at baseline and at 6 hours post-injury. After euthanasia, bilateral kidney tissues were harvested for biochemical and histopathological evaluation.

The main questions this study aimed to answer were:

  • Does dexmedetomidine reduce serum and tissue levels of AKI biomarkers (such as NGAL, KIM-1, TIMP-2, IGFBP7) more effectively than remifentanil in a rat model of crush injury?
  • Are there histological differences in kidney damage between the treatment groups?
  • What is the impact of both drugs on oxidative stress markers (TAC - total antioxidant capacity, TOS - total oxidant status) and renal function parameters such as creatinine and urea?

Biochemical analyses included ELISA-based quantification of NGAL, KIM-1, TIMP-2, IGFBP7, TAC, TOS, serum creatinine, and BUN. Histopathological scoring was performed by a blinded pathologist, assessing tubular necrosis, interstitial edema, and inflammatory cell infiltration.

The study found that rats in the dexmedetomidine group exhibited lower levels of renal injury markers and histopathological damage scores compared to those in the remifentanil group. These findings suggest that dexmedetomidine may offer superior renal protection during acute crush injury compared to remifentanil, potentially via anti-inflammatory and antioxidant mechanisms.

The results of this study may help guide anesthetic drug selection in trauma patients at high risk of kidney injury, and lay the foundation for future translational research.

02

Conditions studied

  • Acute Kidney Injury
  • Crush Injury
  • Rhabdomyolysis

Keywords

  • remifentanil
  • dexmedetomidine
  • crush injury
  • renal injury
  • KIM-1
  • NGAL
03

In context

Acute Kidney Injury

1,595 studies on the registry are indexed under Acute Kidney Injury; 371 are open to participants now.

This study's enrollment of 28 is below the median of 100 across 763 interventional studies indexed under Acute Kidney Injury.

Browse Acute Kidney Injury studies →

Lead sponsor

Ankara City Hospital Bilkent is the lead sponsor of 424 studies on the registry; 105 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Rat Experiment

05

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Single group
Masking
Triple (Care provider, Investigator, Outcomes assessor)
Enrollment
28 participants (actual)

Study arms

  • No intervention
    Control

    The control group did not receive any intervention or pharmacological treatment.

  • Experimental
    Dexmedetomidine

    Following 2 hours of bilateral muscle compression, rats in the dexmedetomidine group underwent a 1-hour period including both laparotomy and continuous intravenous dexmedetomidine infusion.

    Drug: Dexmedetomidine · Procedure: Laparotomy · Procedure: Compression

  • Experimental
    Remifentanil

    Following 2 hours of bilateral muscle compression, rats in the remifentanil group underwent a 1-hour period including both laparotomy and continuous intravenous remifentanil infusion.

    Drug: Remifentanil · Procedure: Laparotomy · Procedure: Compression

  • Sham comparator
    Sham

    In the sham group, bilateral gastrocnemius muscle compression was applied for 2 hours and laparotomy was performed, but no pharmacological intervention was given.

    Procedure: Laparotomy · Procedure: Compression

Interventions

  • DrugDexmedetomidine

    Following 2 hours of bilateral muscle compression, rats in the dexmedetomidine group underwent a 1-hour period including both laparotomy and continuous intravenous dexmedetomidine infusion.

  • DrugRemifentanil

    Following 2 hours of bilateral muscle compression, rats in the remifentanil group underwent a 1-hour period including both laparotomy and continuous intravenous remifentanil infusion.

  • ProcedureLaparotomy

    A standardized laparotomy was carried out for 1 hour, during which the abdominal cavity was opened and subsequently closed. This procedure aimed to mimic the physiological impact of a one-hour surgical operation.

  • ProcedureCompression

    Bilateral compression was applied to the gastrocnemius muscles for a duration of 2 hours.

06

What researchers measure

Primary outcomes

  1. Serum Creatinine Level

    Change in serum creatinine levels measured at 0, 2, and 6 hours after experimental crush injury in Wistar Albino rats receiving either dexmedetomidine or remifentanil. This outcome is used to assess renal function and the nephroprotective effect of the interventions.

    Time frame: Baseline (0 hour), 2 hours, and 6 hours after intervention

Secondary outcomes

  1. Neutrophil Gelatinase-Associated Lipocalin (NGAL) Level

    NGAL levels measured in serum at three time points to assess early renal tubular injury following experimental crush injury and treatment with dexmedetomidine or remifentanil. NGAL is an early biomarker for acute kidney injury (AKI) and reflects renal stress.

    Time frame: 0, 2, and 6 hours after intervention

  2. Histopathological Tubular Injury Score

    Histopathological evaluation of renal tissue samples using scoring for tubular necrosis, brush border loss, dilatation, congestion, and apoptotic cell count. Quantitative damage scoring was performed blindly by two pathologists to compare the nephroprotective effects of dexmedetomidine and remifentanil.

    Time frame: At 6 hours after intervention (after sacrifice)

  3. Kidney Injury Molecule-1 (KIM-1) Level

    Serum levels of KIM-1 measured by ELISA to evaluate renal tubular epithelial injury and compare the protective effects of the two anesthetic agents.

    Time frame: 0, 2, and 6 hours after intervention

  4. TIMP-2) × (IGFBP7) Product Level

    0, 2, and 6 hours after intervention

    Time frame: The combined serum levels of TIMP-2 and IGFBP7, representing G1 cell cycle arrest, were measured to detect early renal stress and predict AKI development in the experimental model.

07

Study locations

1 site
  • Ankara Bilkent City Hospital
    Ankara, Turkey (Türkiye)
08

References and documents

Publications

  • Bao N, Dai D. Dexmedetomidine Protects against Ischemia and Reperfusion-Induced Kidney Injury in Rats. Mediators Inflamm. 2020 Apr 3;2020:2120971. doi: 10.1155/2020/2120971. eCollection 2020. PubMed 32317860 ↗
  • Bywaters EG, Beall D. Crush Injuries with Impairment of Renal Function. Br Med J. 1941 Mar 22;1(4185):427-32. doi: 10.1136/bmj.1.4185.427. No abstract available. PubMed 20783577 ↗
  • Bostankolu E, Ayoglu H, Yurtlu S, Okyay RD, Erdogan G, Deniz Y, Hanci V, Can M, Turan IO. Dexmedetomidine did not reduce the effects of tourniquet-induced ischemia-reperfusion injury during general anesthesia. Kaohsiung J Med Sci. 2013 Feb;29(2):75-81. doi: 10.1016/j.kjms.2012.08.013. Epub 2012 Oct 13. PubMed 23347808 ↗
  • Celikmen MF, Sarikaya S, Ozucelik DN, Sever MS, Aciksari K, Celikmen DM, Yazicioglu M, Kandemir A, Dogan H, Ayvaci BM, Ozasir Abuska D, Sadillioglu S. Effects of acetaminophen and mannitol on crush injuries in rats: An experimental study. Ulus Travma Acil Cerrahi Derg. 2016 Jul;22(4):305-14. doi: 10.5505/tjtes.2015.76824. PubMed 27598600 ↗
  • de Carvalho AL, Vital RB, Kakuda CM, Braz JR, Castiglia YM, Braz LG, Modolo MP, Ribeiro OR, Domingues MA, Modolo NS. Dexmedetomidine on renal ischemia-reperfusion injury in rats: assessment by means of NGAL and histology. Ren Fail. 2015 Apr;37(3):526-30. doi: 10.3109/0886022X.2015.1006118. Epub 2015 Jan 23. PubMed 25613736 ↗
  • Erkilic E, Kesimci E, Alaybeyoglu F, Kilinc I, Tural R, Yazgan A, Gumus T, Sepici Dincel A, Dumlu EG, Kanbak O. Does remifentanil attenuate renal ischemia-reperfusion injury better than dexmedetomidine in rat kidney? Drug Des Devel Ther. 2017 Mar 8;11:677-683. doi: 10.2147/DDDT.S126701. eCollection 2017. PubMed 28331287 ↗
  • Gonullu E, Ozkardesler S, Kume T, Duru LS, Akan M, Guneli ME, Ergur BU, Meseri R, Dora O. Comparison of the effects of dexmedetomidine administered at two different times on renal ischemia/reperfusion injury in rats. Braz J Anesthesiol. 2014 May-Jun;64(3):152-8. doi: 10.1016/j.bjane.2013.06.002. Epub 2013 Oct 16. PubMed 24907872 ↗
  • Kanbak O, Aydogan B, Gumus T. Effects of remifentanil and propofol on distant organ lung injury in an ischemia-reperfusion model. Open Med (Wars). 2021 Nov 8;16(1):1673-1680. doi: 10.1515/med-2021-0381. eCollection 2021. PubMed 34761118 ↗
  • Kocoglu H, Ozturk H, Ozturk H, Yilmaz F, Gulcu N. Effect of dexmedetomidine on ischemia-reperfusion injury in rat kidney: a histopathologic study. Ren Fail. 2009;31(1):70-4. doi: 10.1080/08860220802546487. PubMed 19142813 ↗
  • Sugita S, Okabe T, Sakamoto A. Continuous infusion of dexmedetomidine improves renal ischemia-reperfusion injury in rat kidney. J Nippon Med Sch. 2013;80(2):131-9. doi: 10.1272/jnms.80.131. PubMed 23657066 ↗
  • Si YN, Bao HG, Xu L, Wang XL, Shen Y, Wang JS, Yang XB. Dexmedetomidine protects against ischemia/reperfusion injury in rat kidney. Eur Rev Med Pharmacol Sci. 2014 Jul;18(13):1843-51. PubMed 25010612 ↗

Study documents

  • Protocol and statistical analysis plan · Jul 23, 2025

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — This is a preclinical animal study conducted on Wistar Albino rats. Since no human subjects were enrolled, there is no individual participant data (IPD) to share.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 30, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07094165
Lead sponsor
Ankara City Hospital Bilkent
Responsible party
Sponsor
First posted
Jul 30, 2025
Start date
Jul 10, 2024
Primary completion
Mar 7, 2025
Completion
Mar 10, 2025
Last update
Jul 30, 2025

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jul 2025. You cannot join it, but the record below documents what was studied.

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