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Study · Animal study (in vivo) · mouse · 2026

7 results

A kappa opioid receptor agonist, difelikefalin, improves acute kidney injury in experimental sepsis models.

Sawanobori Y, Nakano D, Kitamura H, Kitada K, Asaga T, Suzuki N, Yamamoto M, Ogino Y, Shirakami G, Nishiyama A

PloS one21 Apr 2026

PMID42013153 (opens in a new tab)PMCIDPMC13098930 (opens in a new tab)DOI10.1371/journal.pone.0343693 (opens in a new tab)PepBankPUB-42013153
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Summary

There is a pressing need for therapies that can lessen the severity of acute kidney injury (AKI) and subsequent critical illness. Difelikefalin, a peripherally acting kappa opioid receptor agonist, shows promise in controlling postoperative pain and chronic kidney disease-associated pruritis. Here, we report that difelikefalin attenuated AKI in experimental mouse models of critical illness. Preconditioning with difelikefalin significantly reduced oliguria in both lipopolysaccharide (LPS)-induced and cecum ligation and puncture-induced models. Moreover, difelikefalin treatment after renal ischemia/reperfusion substantially decreased the LPS-induced mortality rate on day 6 post-ischemia/reperfusion. We hypothesized that the reno-protective effects of difelikefalin are mediated through receptors expressed in either the neural system, immune cells, or the renal parenchyma. Denervation of nerves around the renal pedicle improved urine flow; difelikefalin further enhanced this improvement, regardless of renal denervation. Difelikefalin did not affect plasma cytokine levels after LPS administration at 3 and 6 hours. Renal kappa receptor expression overlapped with the pattern of neural crest-derived interstitial cells. LPS administration tended to increase cytokine expression in isolated renal kappa receptor-positive cells, and difelikefalin suppressed these changes. Overall, difelikefalin demonstrated renal protective effects against AKI in murine endotoxemia and polymicrobial sepsis models and improved survival in post-ischemia/reperfusion endotoxemia.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In mouse critical illness models, difelikefalin attenuated acute kidney injury.

    In plain wordsIn mice with critical illness, difelikefalin reduced acute kidney injury.

    Peptide
    Difelikefalin
    Outcome
    DecreaseAcute kidney injury
    Study

    mousen: not reported in source

    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Here, we report that difelikefalin attenuated AKI in experimental mouse models of critical illness.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In mice with LPS-induced illness, difelikefalin preconditioning significantly reduced oliguria.

    In plain wordsIn mice with LPS-induced illness, difelikefalin reduced low urine output.

    Peptide
    Difelikefalin
    Outcome
    DecreaseOliguria in LPS model
    Study

    mousen: not reported in source

    LPS-induced critical illness
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Preconditioning with difelikefalin significantly reduced oliguria in both lipopolysaccharide (LPS)-induced and cecum ligation and puncture-induced models.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In mice with cecum ligation and puncture, difelikefalin preconditioning significantly reduced oliguria.

    In plain wordsIn mice with cecum ligation and puncture, difelikefalin reduced low urine output.

    Peptide
    Difelikefalin
    Outcome
    DecreaseOliguria in cecum ligation and puncture model
    Study

    mousen: not reported in source

    Cecum ligation and puncture
    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Preconditioning with difelikefalin significantly reduced oliguria in both lipopolysaccharide (LPS)-induced and cecum ligation and puncture-induced models.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In mice after renal ischemia/reperfusion, difelikefalin substantially reduced LPS-induced mortality on day 6.

    In plain wordsIn mice after kidney ischemia/reperfusion, difelikefalin reduced mortality after LPS exposure.

    Peptide
    Difelikefalin
    Outcome
    DecreaseMortality after ischemia/reperfusion and LPS
    Study

    mousen: not reported in source

    Outcome group
    Mortality · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Moreover, difelikefalin treatment after renal ischemia/reperfusion substantially decreased the LPS-induced mortality rate on day 6 post-ischemia/reperfusion.
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In mice, difelikefalin further improved urine flow regardless of renal denervation.

    In plain wordsIn mice, difelikefalin improved urine flow with or without renal denervation.

    Peptide
    Difelikefalin
    Outcome
    IncreaseUrine flow
    Study

    mousen: not reported in source

    Outcome group
    Kidney function · Kidney and urinary
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Denervation of nerves around the renal pedicle improved urine flow; difelikefalin further enhanced this improvement, regardless of renal denervation.
  6. 06AnimalAnimal study (in vivo)Mechanism

    In mice given LPS, difelikefalin did not affect plasma cytokine levels at 3 and 6 hours.

    In plain wordsIn mice given LPS, difelikefalin did not change blood cytokine levels.

    Peptide
    Difelikefalin
    Outcome
    No significant changePlasma cytokines
    Study

    mousen: not reported in source

    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Difelikefalin did not affect plasma cytokine levels after LPS administration at 3 and 6 hours.
  7. 07LabIn vitro (cells)Mechanism

    In isolated renal kappa receptor-positive cells, difelikefalin suppressed LPS-associated cytokine expression changes.

    In plain wordsIn cells, difelikefalin suppressed cytokine expression changes associated with LPS.

    Peptide
    Difelikefalin
    Outcome
    DecreaseCytokine expression in renal receptor-positive cells
    Study

    n: not reported in source

    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    LPS administration tended to increase cytokine expression in isolated renal kappa receptor-positive cells, and difelikefalin suppressed these changes.

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

Terms as the source lists them.

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