title: Prolonged cold ischemia accelerates cellular and humoral chronic rejection in a rat model of kidney allotransplantation.
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.
authors.affiliation: Transplant Research Center, Chiara Cucchi De Alessandri & Gilberto Crespi, Mario Negri Institute for Pharmacological Research, Ranica, Bergamo, Italy.
authors.forename: Samantha
authors.initials: S
authors.lastname: Solini
authors.forename: Sistiana
authors.initials: S
authors.lastname: Aiello
authors.forename: Paola
authors.initials: P
authors.lastname: Cassis
authors.forename: Pierangela
authors.initials: P
authors.lastname: Scudeletti
authors.forename: Nadia
authors.initials: N
authors.lastname: Azzollini
authors.forename: Marilena
authors.initials: M
authors.lastname: Mister
authors.forename: Federica
authors.initials: F
authors.lastname: Rocchetta
authors.forename: Mauro
authors.initials: M
authors.lastname: Abbate
authors.forename: Rafael Luiz
authors.initials: RL
authors.lastname: Pereira
authors.forename: Marina
authors.initials: M
authors.lastname: Noris
mesh_terms: D000818:Animals; D017209:Apoptosis; D050377:Cold Ischemia / Q000009:adverse effects*; D051799:Delayed Graft Function / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology* / Q000379:methods / Q000401:mortality; D008297:Male; D051381:Rats; D011920:Rats, Inbred WF; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology / Q000379:methods / Q000401:mortality