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dc.contributor.authorFerdinand, John R
dc.contributor.authorHosgood, Sarah A
dc.contributor.authorMoore, Tom
dc.contributor.authorFerro, Ashley
dc.contributor.authorWard, Christopher J
dc.contributor.authorCastro-Dopico, Tomas
dc.contributor.authorNicholson, Michael L
dc.contributor.authorClatworthy, Menna R
dc.date.accessioned2020-11-14T00:30:21Z
dc.date.available2020-11-14T00:30:21Z
dc.date.issued2021-06
dc.identifier.issn1600-6135
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/312885
dc.description.abstractTransplantation is the optimal treatment for most patients with end-stage kidney disease but organ shortage is a major challenge. Normothermic machine perfusion (NMP) has been used to recondition marginal organs; however, mechanisms by which NMP might benefit organs are not well understood. Using pairs of human kidneys obtained from the same donor, we compared the effect of NMP with that of cold storage on the global kidney transcriptome. We found that cold storage led to a global reduction in gene expression, including inflammatory pathway genes and those required for energy generation processes, such as oxidative phosphorylation (OXPHOS). In contrast, during NMP, there was marked upregulation OXPHOS genes, but also of a number of immune and inflammatory pathway genes. Using biopsies from kidneys undergoing NMP that were subsequently transplanted, we found that higher inflammatory gene expression occurred in organs with prolonged delayed graft function (DGF). Therefore, we used a hemoadsorber (HA) to remove pro-inflammatory cytokines. This attenuated inflammatory gene expression increased OXPHOS pathway genes and had potentially clinically important effects in reducing the expression of a DGF-associated gene signature. Together, our data suggest that adsorption of pro-inflammatory mediators from the perfusate represents a potential intervention which may improve organ viability.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherWiley
dc.rightsAll rights reserved
dc.subjectKidney
dc.subjectHumans
dc.subjectCytokines
dc.subjectOrgan Preservation
dc.subjectKidney Transplantation
dc.subjectPerfusion
dc.subjectGraft Survival
dc.subjectTissue Donors
dc.subjectDelayed Graft Function
dc.titleCytokine absorption during human kidney perfusion reduces delayed graft function-associated inflammatory gene signature.
dc.typeArticle
prism.endingPage2199
prism.issueIdentifier6
prism.publicationDate2021
prism.publicationNameAm J Transplant
prism.startingPage2188
prism.volume21
dc.identifier.doi10.17863/CAM.59982
dcterms.dateAccepted2020-10-19
rioxxterms.versionofrecord10.1111/ajt.16371
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-06
dc.contributor.orcidFerdinand, John R [0000-0003-0936-0128]
dc.contributor.orcidHosgood, Sarah A [0000-0002-8039-143X]
dc.identifier.eissn1600-6143
rioxxterms.typeJournal Article/Review
pubs.funder-project-idStoneygate Trust (ENVP3)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NIHR201350)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NIHR BTRU-2014-10027)
pubs.funder-project-idMedical Research Council (MR/N024907/1)
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/P020259/1)
cam.issuedOnline2020-11-22
cam.orpheus.successMon Nov 16 07:30:24 GMT 2020 - Embargo updated
rioxxterms.freetoread.startdate2021-10-23


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