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Study · Animal study (in vivo) · rat · 2025

5 results

Anti-inflammatory and renoprotective effects of difelikefalin, a kappa opioid receptor agonist, in a rat model of renal ischemia-reperfusion-induced acute kidney injury.

Takeuchi H, Tatemichi S, Okuhara Y

BMC nephrology1 Jul 2025

PMID40596915 (opens in a new tab)PMCIDPMC12211451 (opens in a new tab)DOI10.1186/s12882-025-04199-9 (opens in a new tab)PepBankPUB-40596915
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Summary

BackgroundThis study evaluated the effects of difelikefalin, a kappa opioid receptor (KOR) agonist, on the inflammatory response and renal dysfunction in a rat model of acute kidney injury induced by renal ischemia-reperfusion injury, comparing it with other KOR agonists.MethodsOne week after right nephrectomy, rats received one of three drugs (difelikefalin, nalfurafine hydrochloride, or U-50488H). Thirty minutes later, ischemia was induced in the left kidney by clamping its artery and vein for 45 min. Rats were then transferred to metabolic cages for 24-h urine collection, and blood was taken at the 24-h time point. Renal function (blood urea nitrogen [BUN], serum creatinine [SCr], and creatinine clearance [CCr]) and 23 serum cytokines were assessed, along with histopathological evaluation of renal tubular damage.ResultsCompared with the sham group, the vehicle group showed increased BUN and SCr levels, reduced CCr, and renal tubular damage. Difelikefalin improved BUN, SCr, and CCr levels and mitigated renal tubular damage. Similar effects were observed with nalfurafine hydrochloride and U-50488H. Thirteen serum cytokines were elevated in the vehicle group. Difelikefalin suppressed all elevated cytokines, U-50488H showed moderate efficacy, and nalfurafine hydrochloride exhibited little inhibitory effect.ConclusionThese findings indicate that difelikefalin has anti-inflammatory and renoprotective effects in a rat acute kidney injury model, with varying anti-inflammatory efficacy among KOR agonists.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

5 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In rats with renal ischemia-reperfusion injury, difelikefalin improved blood urea nitrogen levels.

    In plain wordsIn rats with kidney injury, difelikefalin improved blood urea nitrogen levels.

    Peptide
    Difelikefalin
    Outcome
    DecreaseBlood urea nitrogen
    Study

    ratn: not reported in source

    Renal ischemia-reperfusion-induced acute kidney injury
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Difelikefalin improved BUN, SCr, and CCr levels and mitigated renal tubular damage.
    3 context sentences
    Summary · context
    One week after right nephrectomy, rats received one of three drugs (difelikefalin, nalfurafine hydrochloride, or U-50488H).
    Summary · context
    Thirty minutes later, ischemia was induced in the left kidney by clamping its artery and vein for 45 min.
    Summary · context
    Rats were then transferred to metabolic cages for 24-h urine collection, and blood was taken at the 24-h time point.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In rats with renal ischemia-reperfusion injury, difelikefalin improved serum creatinine levels.

    In plain wordsIn rats with kidney injury, difelikefalin improved serum creatinine levels.

    Peptide
    Difelikefalin
    Outcome
    DecreaseSerum creatinine
    Study

    ratn: not reported in source

    Renal ischemia-reperfusion-induced acute kidney injury
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Difelikefalin improved BUN, SCr, and CCr levels and mitigated renal tubular damage.
    3 context sentences
    Summary · context
    One week after right nephrectomy, rats received one of three drugs (difelikefalin, nalfurafine hydrochloride, or U-50488H).
    Summary · context
    Thirty minutes later, ischemia was induced in the left kidney by clamping its artery and vein for 45 min.
    Summary · context
    Rats were then transferred to metabolic cages for 24-h urine collection, and blood was taken at the 24-h time point.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In rats with renal ischemia-reperfusion injury, difelikefalin improved creatinine clearance.

    In plain wordsIn rats with kidney injury, difelikefalin improved creatinine clearance.

    Peptide
    Difelikefalin
    Outcome
    IncreaseCreatinine clearance
    Study

    ratn: not reported in source

    Renal ischemia-reperfusion-induced acute kidney injury
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Difelikefalin improved BUN, SCr, and CCr levels and mitigated renal tubular damage.
    3 context sentences
    Summary · context
    One week after right nephrectomy, rats received one of three drugs (difelikefalin, nalfurafine hydrochloride, or U-50488H).
    Summary · context
    Thirty minutes later, ischemia was induced in the left kidney by clamping its artery and vein for 45 min.
    Summary · context
    Rats were then transferred to metabolic cages for 24-h urine collection, and blood was taken at the 24-h time point.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In rats with renal ischemia-reperfusion injury, difelikefalin mitigated renal tubular damage.

    In plain wordsIn rats with kidney injury, difelikefalin reduced kidney tubule damage.

    Peptide
    Difelikefalin
    Outcome
    DecreaseRenal tubular damage
    Study

    ratn: not reported in source

    Renal ischemia-reperfusion-induced acute kidney injury
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Difelikefalin improved BUN, SCr, and CCr levels and mitigated renal tubular damage.
    3 context sentences
    Summary · context
    One week after right nephrectomy, rats received one of three drugs (difelikefalin, nalfurafine hydrochloride, or U-50488H).
    Summary · context
    Thirty minutes later, ischemia was induced in the left kidney by clamping its artery and vein for 45 min.
    Summary · context
    Rats were then transferred to metabolic cages for 24-h urine collection, and blood was taken at the 24-h time point.
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In rats with renal ischemia-reperfusion injury, difelikefalin suppressed all thirteen serum cytokines elevated in the vehicle group.

    In plain wordsIn rats with kidney injury, difelikefalin suppressed all elevated serum cytokines.

    Peptide
    Difelikefalin
    Outcome
    DecreaseElevated serum cytokines
    Study

    ratn: not reported in source

    Renal ischemia-reperfusion-induced acute kidney injury
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Difelikefalin suppressed all elevated cytokines, U-50488H showed moderate efficacy, and nalfurafine hydrochloride exhibited little inhibitory effect.
    4 context sentences
    Summary · context
    Thirteen serum cytokines were elevated in the vehicle group.
    Summary · context
    One week after right nephrectomy, rats received one of three drugs (difelikefalin, nalfurafine hydrochloride, or U-50488H).
    Summary · context
    Thirty minutes later, ischemia was induced in the left kidney by clamping its artery and vein for 45 min.
    Summary · context
    Rats were then transferred to metabolic cages for 24-h urine collection, and blood was taken at the 24-h time point.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:35 UTC

    First added · source update from Europe PMC

Subjects

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