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 language | English |
|---|---|
| Pages (from-to) | 347-356 |
| Number of pages | 10 |
| Journal | Transplant International |
| Volume | 25 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2012 |
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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 journal › Article
}
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 -