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 journalArticle

12 Citations (Scopus)

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

Fingerprint

Cold Ischemia
Allografts
Kidney
Isoantigens
Ischemia
B-Lymphocytes
Transplants
Wounds and Injuries
Delayed Graft Function
Pathologic Processes
Proteinuria
Kidney Transplantation
Atrophy
Anti-Idiotypic Antibodies
Fibrosis
Immunoglobulin G
T-Lymphocytes
Mortality

Keywords

  • chronic allograft injury
  • ischemia/reperfusion
  • kidney transplant

ASJC Scopus subject areas

  • Transplantation

Cite this

Prolonged cold ischemia accelerates cellular and humoral chronic rejection in a rat model of kidney allotransplantation. / Solini, Samantha; Aiello, Sistiana; Cassis, Paola; Scudeletti, Pierangela; Azzollini, Nadia; Mister, Marilena; Rocchetta, Federica; Abbate, Mauro; Pereira, Rafael Luiz; Noris, Marina.

In: Transplant International, Vol. 25, No. 3, 03.2012, p. 347-356.

Research output: Contribution to journalArticle

Solini, Samantha ; Aiello, Sistiana ; Cassis, Paola ; Scudeletti, Pierangela ; Azzollini, Nadia ; Mister, Marilena ; Rocchetta, Federica ; Abbate, Mauro ; Pereira, Rafael Luiz ; Noris, Marina. / Prolonged cold ischemia accelerates cellular and humoral chronic rejection in a rat model of kidney allotransplantation. In: Transplant International. 2012 ; Vol. 25, No. 3. pp. 347-356.
@article{2d8756e65af6457db8aafddcd7dda07f,
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.",
keywords = "chronic allograft injury, ischemia/reperfusion, kidney transplant",
author = "Samantha Solini and Sistiana Aiello and Paola Cassis and Pierangela Scudeletti and Nadia Azzollini and Marilena Mister and Federica Rocchetta and Mauro Abbate and Pereira, {Rafael Luiz} and Marina Noris",
year = "2012",
month = "3",
doi = "10.1111/j.1432-2277.2011.01425.x",
language = "English",
volume = "25",
pages = "347--356",
journal = "Transplant International",
issn = "0934-0874",
publisher = "Blackwell Publishing Ltd",
number = "3",

}

TY - JOUR

T1 - Prolonged cold ischemia accelerates cellular and humoral chronic rejection in a rat model of kidney allotransplantation

AU - Solini, Samantha

AU - Aiello, Sistiana

AU - Cassis, Paola

AU - Scudeletti, Pierangela

AU - Azzollini, Nadia

AU - Mister, Marilena

AU - Rocchetta, Federica

AU - Abbate, Mauro

AU - Pereira, Rafael Luiz

AU - Noris, Marina

PY - 2012/3

Y1 - 2012/3

N2 - 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.

AB - 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.

KW - chronic allograft injury

KW - ischemia/reperfusion

KW - kidney transplant

UR - http://www.scopus.com/inward/record.url?scp=84857056196&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857056196&partnerID=8YFLogxK

U2 - 10.1111/j.1432-2277.2011.01425.x

DO - 10.1111/j.1432-2277.2011.01425.x

M3 - Article

VL - 25

SP - 347

EP - 356

JO - Transplant International

JF - Transplant International

SN - 0934-0874

IS - 3

ER -