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

Samantha Solini, Sistiana Aiello, Paola Cassis, Pierangela Scudeletti, Nadia Azzollini, Marilena Mister, Federica Rocchetta, Mauro Abbate, Rafael Luiz Pereira, Marina Noris

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)347-356
Number of pages10
JournalTransplant International
Volume25
Issue number3
DOIs
Publication statusPublished - Mar 2012

Keywords

  • chronic allograft injury
  • ischemia/reperfusion
  • kidney transplant

ASJC Scopus subject areas

  • Transplantation

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