Defining the molecular response to ischemia-reperfusion injury and remote ischemic preconditioning in human kidney transplantation.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2024
2024
Historique:
received:
01
09
2023
accepted:
22
09
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
Ischemia-reperfusion injury (IRI) inevitably occurs during kidney transplantation and extended ischemia is associated with delayed graft function and poor outcomes. Remote ischemic preconditioning (RIPC) is a simple, noninvasive procedure aimed at reducing IRI and improving graft function. Experimental studies have implicated the kynurenine pathway as a protective mechanism behind RIPC. First, paired biopsies from 11 living kidney donors were analyzed to characterize the acute transcriptomic response to IRI. Second, 16 living kidney donors were subjected to either RIPC (n = 9) or no pretreatment (n = 7) to evaluate the impact of RIPC on the transcriptomic response to IRI. Finally, the effect of RIPC on plasma metabolites was analyzed in 49 healthy subjects. There was a robust immediate response to IRI in the renal transcriptomes of living-donor kidney transplantation, including activation of the mitogen-activated protein kinase (MAPK) and epidermal growth factor receptor (EGFR) pathways. Preconditioning with RIPC did not significantly alter the transcriptomic response to IRI or the concentration of plasma metabolites. The present data validate living-donor kidney transplantation as a suitable model for mechanistic studies of IRI in human kidneys. The failure of RIPC to alter transcriptomic responses or metabolites in the kynurenine pathway raises the question of the robustness of the standard procedure used to induce RIPC, and might explain the mixed results in clinical trials evaluating RIPC as a method to attenuate IRI.
Sections du résumé
BACKGROUND
BACKGROUND
Ischemia-reperfusion injury (IRI) inevitably occurs during kidney transplantation and extended ischemia is associated with delayed graft function and poor outcomes. Remote ischemic preconditioning (RIPC) is a simple, noninvasive procedure aimed at reducing IRI and improving graft function. Experimental studies have implicated the kynurenine pathway as a protective mechanism behind RIPC.
METHODS
METHODS
First, paired biopsies from 11 living kidney donors were analyzed to characterize the acute transcriptomic response to IRI. Second, 16 living kidney donors were subjected to either RIPC (n = 9) or no pretreatment (n = 7) to evaluate the impact of RIPC on the transcriptomic response to IRI. Finally, the effect of RIPC on plasma metabolites was analyzed in 49 healthy subjects.
RESULTS
RESULTS
There was a robust immediate response to IRI in the renal transcriptomes of living-donor kidney transplantation, including activation of the mitogen-activated protein kinase (MAPK) and epidermal growth factor receptor (EGFR) pathways. Preconditioning with RIPC did not significantly alter the transcriptomic response to IRI or the concentration of plasma metabolites.
CONCLUSIONS
CONCLUSIONS
The present data validate living-donor kidney transplantation as a suitable model for mechanistic studies of IRI in human kidneys. The failure of RIPC to alter transcriptomic responses or metabolites in the kynurenine pathway raises the question of the robustness of the standard procedure used to induce RIPC, and might explain the mixed results in clinical trials evaluating RIPC as a method to attenuate IRI.
Identifiants
pubmed: 39471208
doi: 10.1371/journal.pone.0311613
pii: PONE-D-23-20971
pmc: PMC11521294
doi:
Substances chimiques
Kynurenine
343-65-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0311613Informations de copyright
Copyright: © 2024 Nordström et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
J.S.R. reports funding from GSK and Sanofi and fees from Travere Therapeutics and Astex. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development, or marketed products associated with this research to declare.
Références
Bioinform Adv. 2022 Mar 08;2(1):vbac016
pubmed: 36699385
Pflugers Arch. 2022 Mar;474(3):343-353
pubmed: 34989875
JCI Insight. 2018 Nov 15;3(22):
pubmed: 30429361
PLoS One. 2013;8(2):e56224
pubmed: 23418539
MDM Policy Pract. 2018 Jun 17;3(1):2381468318781811
pubmed: 30288451
J Biol Chem. 2001 Apr 13;276(15):11870-6
pubmed: 11150293
Nat Commun. 2018 Jan 2;9(1):20
pubmed: 29295995
Anal Chim Acta. 2016 Sep 14;936:149-56
pubmed: 27566350
J Clin Med. 2019 May 20;8(5):
pubmed: 31137470
Front Physiol. 2020 May 27;11:510
pubmed: 32581828
Nephron. 2018;140(2):94-98
pubmed: 30007955
N Engl J Med. 2015 Oct 8;373(15):1397-407
pubmed: 26436208
Front Pharmacol. 2021 Feb 19;12:598959
pubmed: 33679395
Mol Med Rep. 2016 Jan;13(1):9-12
pubmed: 26548643
J Am Heart Assoc. 2017 Feb 20;6(2):
pubmed: 28219918
Cell. 2016 Feb 25;164(5):884-95
pubmed: 26919427
J Biol Chem. 1994 Oct 21;269(42):26546-51
pubmed: 7929379
J Cereb Blood Flow Metab. 2009 Aug;29(8):1454-62
pubmed: 19436313
Circulation. 1993 Mar;87(3):893-9
pubmed: 7680290
Kidney Int. 1999 Feb;55(2):713-23
pubmed: 9987096
Br J Anaesth. 2019 Nov;123(5):584-591
pubmed: 31521337
Genome Res. 2019 Aug;29(8):1363-1375
pubmed: 31340985
Circ Res. 2017 Mar 3;120(5):862-875
pubmed: 27932512
Anesth Analg. 2022 Mar 1;134(3):592-605
pubmed: 34748518
Yonsei Med J. 2022 Apr;63(4):389-398
pubmed: 35352891
J Am Soc Nephrol. 2009 Aug;20(8):1754-64
pubmed: 19470675
Biochim Biophys Acta. 2013 Dec;1832(12):1998-2008
pubmed: 23851027