Targeted donor complement blockade after brain death prevents delayed graft function in a nonhuman primate model of kidney transplantation.
animal models: nonhuman primate
complement biology
delayed graft function (DGF)
donors and donation: donation after brain death (DBD)
immunosuppression/immune modulation
ischemia reperfusion injury (IRI)
kidney transplantation/nephrology
translational research/science
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
23
07
2019
revised:
05
12
2019
accepted:
22
12
2019
pubmed:
11
1
2020
medline:
22
6
2021
entrez:
11
1
2020
Statut:
ppublish
Résumé
Delayed graft function (DGF) in renal transplant is associated with reduced graft survival and increased immunogenicity. The complement-driven inflammatory response after brain death (BD) and posttransplant reperfusion injury play significant roles in the pathogenesis of DGF. In a nonhuman primate model, we tested complement-blockade in BD donors to prevent DGF and improve graft survival. BD donors were maintained for 20 hours; kidneys were procured and stored at 4°C for 43-48 hours prior to implantation into ABO-compatible, nonsensitized, MHC-mismatched recipients. Animals were divided into 3 donor-treatment groups: G1 - vehicle, G2 - rhC1INH+heparin, and G3 - heparin. G2 donors showed significant reduction in classical complement pathway activation and decreased levels of tumor necrosis factor α and monocyte chemoattractant protein 1. DGF was diagnosed in 4/6 (67%) G1 recipients, 3/3 (100%) G3 recipients, and 0/6 (0%) G2 recipients (P = .008). In addition, G2 recipients showed superior renal function, reduced sC5b-9, and reduced urinary neutrophil gelatinase-associated lipocalin in the first week posttransplant. We observed no differences in incidence or severity of graft rejection between groups. Collectively, the data indicate that donor-management targeting complement activation prevents the development of DGF. Our results suggest a pivotal role for complement activation in BD-induced renal injury and postulate complement blockade as a promising strategy for the prevention of DGF after transplantation.
Identifiants
pubmed: 31922336
doi: 10.1111/ajt.15777
pmc: PMC7261643
mid: NIHMS1067601
pii: S1600-6135(22)22352-1
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1513-1526Subventions
Organisme : NIAID NIH HHS
ID : T32 AI125231
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI119140
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI110617
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007665
Pays : United States
Organisme : NIH HHS
ID : P51 OD011106
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.
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