Pharmacologic targeting of renal ischemia-reperfusion injury using a normothermic machine perfusion platform.

Animals Antibodies / pharmacology Blood Urea Nitrogen CD47 Antigen / immunology Chemokines / genetics Complement C3 / metabolism Complement C9 / metabolism Creatinine / blood Drug Delivery Systems Epithelial Cells / drug effects Female Hepatitis A Virus Cellular Receptor 1 / genetics Hydrogen Peroxide / metabolism Inflammation Mediators / metabolism Kidney / pathology Kidney Tubules / pathology Male Mice Mice, Inbred C57BL Neutrophils / drug effects Oxidative Stress / drug effects Perfusion RNA, Messenger / genetics Receptors, Complement / metabolism Reperfusion Injury / blood Swine Temperature

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
24 04 2020
Historique:
received: 25 06 2019
accepted: 27 03 2020
entrez: 26 4 2020
pubmed: 26 4 2020
medline: 1 12 2020
Statut: epublish

Résumé

Normothermic machine perfusion (NMP) is an emerging modality for kidney preservation prior to transplantation. NMP may allow directed pharmacomodulation of renal ischemia-reperfusion injury (IRI) without the need for systemic donor/recipient therapies. Three proven anti-IRI agents not in widespread clinical use, CD47-blocking antibody (αCD47Ab), soluble complement receptor 1 (sCR1), and recombinant thrombomodulin (rTM), were compared in a murine model of kidney IRI. The most effective agent was then utilized in a custom NMP circuit for the treatment of isolated porcine kidneys, ascertaining the impact of the drug on perfusion and IRI-related parameters. αCD47Ab conferred the greatest protection against IRI in mice after 24 hours. αCD47Ab was therefore chosen as the candidate agent for addition to the NMP circuit. CD47 receptor binding was demonstrated by immunofluorescence. Renal perfusion/flow improved with CD47 blockade, with a corresponding reduction in oxidative stress and histologic damage compared to untreated NMP kidneys. Tubular and glomerular functional parameters were not significantly impacted by αCD47Ab treatment during NMP. In a murine renal IRI model, αCD47Ab was confirmed as a superior anti-IRI agent compared to therapies targeting other pathways. NMP enabled effective, direct delivery of this drug to porcine kidneys, although further efficacy needs to be proven in the transplantation setting.

Identifiants

DOI: 10.1038/s41598-020-63687-0 PMID: 32332767 PMC: PMC7181764
pubmed: 32332767
doi: 10.1038/s41598-020-63687-0
pii: 10.1038/s41598-020-63687-0
pmc: PMC7181764
doi:

Substances chimiques

Antibodies 0
CD47 Antigen 0
Chemokines 0
Complement C3 0
Complement C9 0
Havcr1 protein, mouse 0
Hepatitis A Virus Cellular Receptor 1 0
Inflammation Mediators 0
RNA, Messenger 0
Receptors, Complement 0
Creatinine AYI8EX34EU
Hydrogen Peroxide BBX060AN9V

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6930

Subventions

Organisme : British Heart Foundation
ID : FS/19/24/34262
Pays : United Kingdom

Références

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Auteurs

Ahmer M Hameed (AM)

Department of Surgery, Westmead Hospital, Sydney, Australia.
Westmead Institute for Medical Research, Sydney, Australia.
Sydney Medical School, University of Sydney, Sydney, Australia.

David B Lu (DB)

Westmead Institute for Medical Research, Sydney, Australia.

Heather Burns (H)

Westmead Institute for Medical Research, Sydney, Australia.

Nicole Byrne (N)

Westmead Institute for Medical Research, Sydney, Australia.

Yi Vee Chew (YV)

Westmead Institute for Medical Research, Sydney, Australia.
ORCID: 0000-0003-1484-8654

Sohel Julovi (S)

Westmead Institute for Medical Research, Sydney, Australia.

Kedar Ghimire (K)

Westmead Institute for Medical Research, Sydney, Australia.
ORCID: 0000-0002-4672-5256

Negar Talaei Zanjani (NT)

Westmead Institute for Medical Research, Sydney, Australia.

Chow H P'ng (CH)

Institute for Clinical Pathology and Medical Research, Westmead Hospital, Sydney, Australia.

Daniel Meijles (D)

St George's, University of London, London, UK.

Suat Dervish (S)

Westmead Institute for Medical Research, Sydney, Australia.

Ross Matthews (R)

Department of Animal Care, Westmead Hospital, Sydney, Australia.

Ray Miraziz (R)

Department of Anesthesia, Westmead Hospital, Sydney, Australia.

Greg O'Grady (G)

Department of Surgery, The University of Auckland, Auckland, New Zealand.

Lawrence Yuen (L)

Department of Surgery, Westmead Hospital, Sydney, Australia.
Sydney Medical School, University of Sydney, Sydney, Australia.

Henry C Pleass (HC)

Department of Surgery, Westmead Hospital, Sydney, Australia.
Sydney Medical School, University of Sydney, Sydney, Australia.

Natasha M Rogers (NM)

Westmead Institute for Medical Research, Sydney, Australia. natasha.rogers@sydney.edu.au.
Sydney Medical School, University of Sydney, Sydney, Australia. natasha.rogers@sydney.edu.au.
Department of Transplant/Renal Medicine, Westmead Hospital, Sydney, Australia. natasha.rogers@sydney.edu.au.

Wayne J Hawthorne (WJ)

Department of Surgery, Westmead Hospital, Sydney, Australia. wayne.hawthorne@sydney.edu.au.
Westmead Institute for Medical Research, Sydney, Australia. wayne.hawthorne@sydney.edu.au.
Sydney Medical School, University of Sydney, Sydney, Australia. wayne.hawthorne@sydney.edu.au.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Pharmacologic targeting of renal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Pharmacologic targeting of renal...
questionsmedicales.fr › Techniques d'investigation › Techniques de laboratoire clinique › Tests de chimie clinique › Analyse chimique du sang › Azote uréique sanguin › Pharmacologic targeting of renal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Glycoprotéines membranaires › Antigènes CD47 › Pharmacologic targeting of renal...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Chimiokines › Pharmacologic targeting of renal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du sang › Immunoprotéines › Protéines du système du complément › Complément C3 › Pharmacologic targeting of renal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du sang › Immunoprotéines › Protéines du système du complément › Complément C9 › Pharmacologic targeting of renal...
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questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs viraux › Récepteur cellulaire-1 du virus de l'hépatite A › Pharmacologic targeting of renal...
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questionsmedicales.fr › Phénomènes physiologiques › Stress physiologique › Stress oxydatif › Pharmacologic targeting of renal...
questionsmedicales.fr › Techniques d'investigation › Perfusion › Pharmacologic targeting of renal...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Pharmacologic targeting of renal...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs au complément › Pharmacologic targeting of renal...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Complications postopératoires › Lésion d'ischémie-reperfusion › Pharmacologic targeting of renal...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Artiodactyla › Suidae › Pharmacologic targeting of renal...
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