Prompt Thrombo-Inflammatory Response to Ischemia-Reperfusion Injury and Kidney Transplant Outcomes
Strandberg, Gabriel LU ; Öberg, Carl M. LU ; Blom, Anna M. LU
; Slivca, Oleg
LU
; Berglund, David
; Segelmark, Mårten
LU
; Nilsson, Bo
and Biglarnia, Ali Reza
(2023)
In Kidney International Reports
8(12).
p.2592-2602
- Abstract
Introduction: In kidney transplantation (KT), the role of the intravascular innate immune system (IIIS) in response to ischemia-reperfusion injury (IRI) is not well-understood. Here, we studied parallel changes in the generation of key activation products of the proteolytic cascade systems of the IIIS following living donor (LD) and deceased donor (DD) transplantation and evaluated potential associations with clinical outcomes. Methods: In a cohort study, 63 patients undergoing LD (n = 26) and DD (n = 37) transplantation were prospectively included. Fifteen DD kidneys were preserved with hypothermic machine perfusion (HMP), and the remaining were cold stored. Activation products of the kallikrein-kinin, coagulation, and complement... (More)
Introduction: In kidney transplantation (KT), the role of the intravascular innate immune system (IIIS) in response to ischemia-reperfusion injury (IRI) is not well-understood. Here, we studied parallel changes in the generation of key activation products of the proteolytic cascade systems of the IIIS following living donor (LD) and deceased donor (DD) transplantation and evaluated potential associations with clinical outcomes. Methods: In a cohort study, 63 patients undergoing LD (n = 26) and DD (n = 37) transplantation were prospectively included. Fifteen DD kidneys were preserved with hypothermic machine perfusion (HMP), and the remaining were cold stored. Activation products of the kallikrein-kinin, coagulation, and complement systems were measured in blood samples obtained systemically at baseline and locally from the transplant renal vein at 1, 10, and 30 minutes after reperfusion. Results: DD kidneys exhibited a prompt and interlinked activation of all 3 cascade systems of IIIS postreperfusion, indicating a robust and local thrombo-inflammatory response to IRI. In this initial response, the complement activation product sC5b-9 exhibited a robust correlation with other IIIS activation markers and displayed a strong association with short-term and mid-term (24-month) graft dysfunction. In contrast, LD kidneys did not exhibit this thrombo-inflammatory response. The use of HMP was associated with reduced thromboinflammation and preserved mid-term kidney function. Conclusion: Kidneys from DD are vulnerable to a prompt thrombo-inflammatory response to IRI, which adversely affects both short-term and long-term allograft function. Strategies aimed at minimizing graft immunogenicity prior to reperfusion are crucial to mitigate the intricate inflammatory response to IRI.
(Less)
- author
- Strandberg, Gabriel
LU
; Öberg, Carl M.
LU
; Blom, Anna M.
LU
; Slivca, Oleg
LU
; Berglund, David
; Segelmark, Mårten
LU
; Nilsson, Bo
and Biglarnia, Ali Reza
- organization
-
- Surgery (research group)
- Nephrology
- Renal physiology and peritoneal dialysis (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- Department of Translational Medicine
- Protein Chemistry, Malmö (research group)
- Teachers at the Medical Programme
- Autoimmunity and kidney diseases (research group)
- publishing date
- 2023-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- delayed graft function, intravascular innate immune system, ischemia-reperfusion injury, kidney transplantation, organ preservation, thromboinflammation
- in
- Kidney International Reports
- volume
- 8
- issue
- 12
- pages
- 11 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:38106604
- scopus:85174455474
- ISSN
- 2468-0249
- DOI
- 10.1016/j.ekir.2023.09.025
- language
- English
- LU publication?
- yes
- id
- 38b19373-1504-4efb-96da-5edb773fa99e
- date added to LUP
- 2023-12-14 14:48:50
- date last changed
- 2024-04-13 06:54:40
@article{38b19373-1504-4efb-96da-5edb773fa99e,
abstract = {{<p>Introduction: In kidney transplantation (KT), the role of the intravascular innate immune system (IIIS) in response to ischemia-reperfusion injury (IRI) is not well-understood. Here, we studied parallel changes in the generation of key activation products of the proteolytic cascade systems of the IIIS following living donor (LD) and deceased donor (DD) transplantation and evaluated potential associations with clinical outcomes. Methods: In a cohort study, 63 patients undergoing LD (n = 26) and DD (n = 37) transplantation were prospectively included. Fifteen DD kidneys were preserved with hypothermic machine perfusion (HMP), and the remaining were cold stored. Activation products of the kallikrein-kinin, coagulation, and complement systems were measured in blood samples obtained systemically at baseline and locally from the transplant renal vein at 1, 10, and 30 minutes after reperfusion. Results: DD kidneys exhibited a prompt and interlinked activation of all 3 cascade systems of IIIS postreperfusion, indicating a robust and local thrombo-inflammatory response to IRI. In this initial response, the complement activation product sC5b-9 exhibited a robust correlation with other IIIS activation markers and displayed a strong association with short-term and mid-term (24-month) graft dysfunction. In contrast, LD kidneys did not exhibit this thrombo-inflammatory response. The use of HMP was associated with reduced thromboinflammation and preserved mid-term kidney function. Conclusion: Kidneys from DD are vulnerable to a prompt thrombo-inflammatory response to IRI, which adversely affects both short-term and long-term allograft function. Strategies aimed at minimizing graft immunogenicity prior to reperfusion are crucial to mitigate the intricate inflammatory response to IRI.</p>}},
author = {{Strandberg, Gabriel and Öberg, Carl M. and Blom, Anna M. and Slivca, Oleg and Berglund, David and Segelmark, Mårten and Nilsson, Bo and Biglarnia, Ali Reza}},
issn = {{2468-0249}},
keywords = {{delayed graft function; intravascular innate immune system; ischemia-reperfusion injury; kidney transplantation; organ preservation; thromboinflammation}},
language = {{eng}},
number = {{12}},
pages = {{2592--2602}},
publisher = {{Elsevier}},
series = {{Kidney International Reports}},
title = {{Prompt Thrombo-Inflammatory Response to Ischemia-Reperfusion Injury and Kidney Transplant Outcomes}},
url = {{http://dx.doi.org/10.1016/j.ekir.2023.09.025}},
doi = {{10.1016/j.ekir.2023.09.025}},
volume = {{8}},
year = {{2023}},
}