Prolonged cold ischemia accelerates cellular and humoral chronic rejection in a rat model of kidney allotransplantation

Prolonged cold ischemia accelerates cellular and humoral chronic rejection in a rat model of kidney allotransplantation

Author Solini, Samantha Google Scholar
Aiello, Sistiana Google Scholar
Cassis, Paola Google Scholar
Scudeletti, Pierangela Google Scholar
Azzollini, Nadia Google Scholar
Mister, Marilena Google Scholar
Rocchetta, Federica Google Scholar
Abbate, Mauro Google Scholar
Pereira, Rafael Luiz Autor UNIFESP Google Scholar
Noris, Marina Google Scholar
Institution Mario Negri Inst Pharmacol Res
Ctr Anna Maria Astori
Universidade Federal de São Paulo (UNIFESP)
Abstract One of the leading causes of long-term kidney graft loss is chronic allograft injury (CAI), a pathological process triggered by alloantigen-dependent and alloantigen-independent factors. Alloantigen-independent factors, such as cold ischemia (CI) may amplify the recipient immune response against the graft. We investigated the impact of prolonged cold ischemia and the subsequent delayed graft function on CAI in a fully MHC-mismatched rat model of kidney allotransplantation. Prolonged CI was associated with anticipation of proteinuria onset and graft function deterioration (ischemia: 90d; no ischemia: 150d), more severe tubular atrophy, interstitial fibrosis, and glomerulosclerosis, and increased mortality rate (180d survival, ischemia: 0%; no ischemia: 67%). in ischemic allografts, T and B cells were detected very early and were organized in inflammatory clusters. Higher expression of BAFF-R and TACI within the ischemic allografts indicates that B cells are mature and activated. As a consequence of B cell activity, anti-donor antibodies, glomerular C4d and IgG deposition, important features of chronic humoral rejection, appeared earlier in ischemic than in non-ischemic allograft recipients. Thus, prolonged CI time plays a main role in CAI development by triggering acceleration of cellular and humoral reactions of chronic rejection. Limiting CI time should be considered as a main target in kidney transplantation.
Keywords chronic allograft injury
ischemia
reperfusion
kidney transplant
Language English
Sponsor Fondazione ART per la Ricerca sui Trapianti ONLUS (ART, Milan, Italy)
Fondazione ART per la Ricerca sui Trapianti, Milano
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number CNPq: 3093107
Date 2012-03-01
Published in Transplant International. Malden: Wiley-Blackwell, v. 25, n. 3, p. 347-356, 2012.
ISSN 0934-0874 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 347-356
Origin http://dx.doi.org/10.1111/j.1432-2277.2011.01425.x
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000299924900018
URI http://repositorio.unifesp.br/handle/11600/34641

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