Evaluating the effects of subnormothermic perfusion with ap39 in a novel blood‐free model of ex vivo kidney preservation and reperfusion
dc.contributor.author | Juriasingani, S | |
dc.contributor.author | Jackson, A | |
dc.contributor.author | Zhang, MY | |
dc.contributor.author | Ruthirakanthan, A | |
dc.contributor.author | Dugbartey, GJ | |
dc.contributor.author | Sogutdelen, E | |
dc.contributor.author | Levine, M | |
dc.contributor.author | Mandurah, M | |
dc.contributor.author | Whiteman, M | |
dc.contributor.author | Luke, P | |
dc.contributor.author | Sener, A | |
dc.date.accessioned | 2021-07-13T12:33:05Z | |
dc.date.issued | 2021-07-02 | |
dc.description.abstract | The use of blood for normothermic and subnormothermic kidney preservation hinders the translation of these approaches and promising therapeutics. This study evaluates whether adding hydrogen sulfide donor AP39 to Hemopure, a blood substitute, during subnormothermic perfusion improves kidney outcomes. After 30 min of renal pedicle clamping, porcine kidneys were treated to 4 h of static cold storage (SCS‐4 °C) or subnormothermic perfusion at 21 °C with Hemopure (H‐21 °C), Hemopure + 200 nM AP39 (H200nM‐21 °C) or Hemopure + 1 μM AP39 (H1μM‐21 °C). Then, kidneys were reperfused with Hemopure at 37 °C for 4 h with metabolic support. Perfusate composition, tissue oxygenation, urinalysis and histopathology were analyzed. During preservation, the H200nM‐21 °C group exhibited significantly higher urine output than the other groups and significantly higher tissue oxygenation than the H1μM‐21 °C group at 1 h and 2h. During reperfusion, the H200nM‐21 °C group exhibited significantly higher urine output and lower urine protein than the other groups. Additionally, the H200nM‐21 °C group exhibited higher perfusate pO2 levels than the other groups and significantly lower apoptotic injury than the H‐21 °C and the H1μM‐21 °C groups. Thus, subnormothermic perfusion at 21 °C with Hemopure + 200 nM AP39 improves renal outcomes. Additionally, our novel blood‐free model of ex vivo kidney preservation and reperfusion could be useful for studying other therapeutics. | en_GB |
dc.description.sponsorship | Physicians Services Incorporated (PSI) Foundation | en_GB |
dc.description.sponsorship | Kidney Foundation of Canada | en_GB |
dc.identifier.citation | Vol. 22 (13), article 7180 | en_GB |
dc.identifier.doi | 10.3390/ijms22137180 | |
dc.identifier.grantnumber | 18-17 | en_GB |
dc.identifier.grantnumber | 180015 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/126390 | |
dc.language.iso | en | en_GB |
dc.publisher | MDPI | en_GB |
dc.rights | © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | en_GB |
dc.subject | kidney preservation | en_GB |
dc.subject | kidney transplantation | en_GB |
dc.subject | hydrogen sulfide (H2S) | en_GB |
dc.subject | AP39 | en_GB |
dc.subject | donation after cardiac death (DCD) | en_GB |
dc.subject | subnormothermic | en_GB |
dc.title | Evaluating the effects of subnormothermic perfusion with ap39 in a novel blood‐free model of ex vivo kidney preservation and reperfusion | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2021-07-13T12:33:05Z | |
dc.identifier.issn | 1661-6596 | |
dc.description | This is the final version. Available on open access from MDPI via the DOI in this record | en_GB |
dc.description | Data Availability Statement: The data presented in this study are available on request from the corresponding author. | en_GB |
dc.identifier.journal | International Journal of Molecular Sciences | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2021-06-28 | |
exeter.funder | ::Medical Research Council (MRC) | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2021-07-02 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2021-07-13T12:27:30Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2021-07-13T12:33:14Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).