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Pharmacologic targeting of renal ischemia-reperfusion injury using a normothermic machine perfusion platform.
Hameed, Ahmer M; Lu, David B; Burns, Heather; Byrne, Nicole; Chew, Yi Vee; Julovi, Sohel; Ghimire, Kedar; Zanjani, Negar Talaei; P'ng, Chow H; Meijles, Daniel; Dervish, Suat; Matthews, Ross; Miraziz, Ray; O'Grady, Greg; Yuen, Lawrence; Pleass, Henry C; Rogers, Natasha M; Hawthorne, Wayne J.
Affiliation
  • Hameed AM; Department of Surgery, Westmead Hospital, Sydney, Australia.
  • Lu DB; Westmead Institute for Medical Research, Sydney, Australia.
  • Burns H; Sydney Medical School, University of Sydney, Sydney, Australia.
  • Byrne N; Westmead Institute for Medical Research, Sydney, Australia.
  • Chew YV; Westmead Institute for Medical Research, Sydney, Australia.
  • Julovi S; Westmead Institute for Medical Research, Sydney, Australia.
  • Ghimire K; Westmead Institute for Medical Research, Sydney, Australia.
  • Zanjani NT; Westmead Institute for Medical Research, Sydney, Australia.
  • P'ng CH; Westmead Institute for Medical Research, Sydney, Australia.
  • Meijles D; Westmead Institute for Medical Research, Sydney, Australia.
  • Dervish S; Institute for Clinical Pathology and Medical Research, Westmead Hospital, Sydney, Australia.
  • Matthews R; St George's, University of London, London, UK.
  • Miraziz R; Westmead Institute for Medical Research, Sydney, Australia.
  • O'Grady G; Department of Animal Care, Westmead Hospital, Sydney, Australia.
  • Yuen L; Department of Anesthesia, Westmead Hospital, Sydney, Australia.
  • Pleass HC; Department of Surgery, The University of Auckland, Auckland, New Zealand.
  • Rogers NM; Department of Surgery, Westmead Hospital, Sydney, Australia.
  • Hawthorne WJ; Sydney Medical School, University of Sydney, Sydney, Australia.
Sci Rep ; 10(1): 6930, 2020 04 24.
Article in En | MEDLINE | ID: mdl-32332767
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Perfusion / Temperature / Reperfusion Injury / Kidney / Antibodies Limits: Animals Language: En Journal: Sci Rep Year: 2020 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Perfusion / Temperature / Reperfusion Injury / Kidney / Antibodies Limits: Animals Language: En Journal: Sci Rep Year: 2020 Document type: Article