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The neglectable impact of delayed graft function on long-term graft survival in kidneys donated after circulatory death associates with superior organ resilience
Objective: To explore putative different impacts of delayed graft function
(DGF) on long-term graft survival in kidneys donated after brain death (DBD)
and circulatory death (DCD).
Background: Despite a 3-fold higher incidence of DGF in DCD grafts, large
studies show equivalent long-term graft survival for DBD and DCD grafts.
This observation implies a differential impact of DGF on DBD and DCD graft
survival. The contrasting impact is remarkable and yet unexplained.
Methods: The impact of DGF on DBD and DCD graft survival was evaluated
in 6635 kidney transplants performed in The Netherlands. DGF severity and
functional recovery dynamics were assessed for 599 kidney transplants
performed at the Leiden Transplant Center. Immunohistochemical staining,
gene expression profiling, and Ingenuity Pathway Analysis were used to
identify...
Show moreObjective: To explore putative different impacts of delayed graft function
(DGF) on long-term graft survival in kidneys donated after brain death (DBD)
and circulatory death (DCD).
Background: Despite a 3-fold higher incidence of DGF in DCD grafts, large
studies show equivalent long-term graft survival for DBD and DCD grafts.
This observation implies a differential impact of DGF on DBD and DCD graft
survival. The contrasting impact is remarkable and yet unexplained.
Methods: The impact of DGF on DBD and DCD graft survival was evaluated
in 6635 kidney transplants performed in The Netherlands. DGF severity and
functional recovery dynamics were assessed for 599 kidney transplants
performed at the Leiden Transplant Center. Immunohistochemical staining,
gene expression profiling, and Ingenuity Pathway Analysis were used to
identify differentially activated pathways in DBD and DCD grafts.
Results: While DGF severely impacted 10-year graft survival in DBD grafts
(HR 1.67; P < 0.001), DGF did not impact graft survival in DCD grafts (HR
1.08; P ¼ 0.63). Shorter dialysis periods and superior posttransplant eGFRs in
DBD grafts show that the differential impact was not caused by a more severe
DGF phenotype in DBD grafts. Immunohistochemical evaluation indicates
that pathways associated with tissue resilience are present in kidney grafts.
Molecular evaluation showed selective activation of resilience-associated
pathways in DCD grafts.
Conclusions: This study shows an absent impact of DGF on long-term graft
survival in DCD kidneys. Molecular evaluation suggests that the differential
impact of DGF between DBD and DCD grafts relates to donor-type specific
activation of resilience pathways in DCD grafts.
- All authors
- Kok, M.J. de; McGuinness, D.; Shiels, P.G.; Vries, D.K. de; Nolthenius, J.B.T.; Wijermars, L.G.; Rabelink, T.J.; Verschuren, L.; Stevenson, K.S.; Kingsmore, D.B.; McBride, M.; Ploeg, R.J.; Bastiaannet, E.; Schaapherder, A.F.; Lindeman, J.H.
- Date
- 2019-11-01
- Journal
- Annals of Surgery
- Volume
- 270
- Issue
- 5
- Pages
- 877 - 883