Efficiency of Trimetazidine in Renal Dysfunction Secondary to Cold Ischemia–Reperfusion Injury: A Proposed Addition to University of Wisconsin Solution

Cryobiology ◽  
1998 ◽  
Vol 37 (3) ◽  
pp. 231-244 ◽  
Author(s):  
Thierry Hauet ◽  
Claudine Tallineau ◽  
Jean-Michel Goujon ◽  
Michel Carretier ◽  
Michel Eugene ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Renal Dysfunction ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cold Ischemia ◽  
University Of Wisconsin Solution ◽  
University Of Wisconsin ◽  
Wisconsin Solution

scholarly journals Trimetazidine Reduces Renal Dysfunction by Limiting the Cold Ischemia/Reperfusion Injury in Autotransplanted Pig Kidneys

2000 ◽  
Vol 11 (1) ◽  
pp. 138-148
Author(s):  
THIERRY HAUET ◽  
JEAN-MICHEL GOUJON ◽  
ALAIN VANDEWALLE ◽  
HERVE BAUMERT ◽  
LOUIS LACOSTE ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Kidney ◽  
Graft Function ◽  
Renal Medulla ◽  
Cold Ischemia ◽  
University Of Wisconsin ◽  
Preservation Solutions ◽  
Transplanted Kidneys

Abstract. Ischemia/reperfusion injury leads to delayed graft function, which is a major problem in kidney transplantation. This study investigated the effects of adding trimetazidine (TMZ) to the perfusate of cold-stored kidneys on the function of reperfused autotransplanted pig kidney. The left kidney was removed and cold-flushed with Euro-Collins (EC), or University of Wisconsin (UW) solutions with or without 10-6M TMZ and stored for 48 h at 4°C. The kidneys were then autotransplanted and the contralateral kidneys were removed. Several parameters were analyzed over the 14 d after transplantation. The survival rate was 57% in pigs transplanted with kidneys cold-flushed with UW and 43% for those flushed with EC solution; it was 100% for pigs having kidneys cold-flushed with TMZ-supplemented UW and EC solutions. The functions of the transplanted kidneys were also better preserved after cold flush with TMZ-supplemented solutions than with TMZ-free solutions. Creatinine clearance was higher and the urinary excretion of trimethylamine-N-oxide and dimethylamine, used as markers of renal medulla injury, were lower in animals transplanted with kidneys cold-flushed with TMZ-supplemented solutions than with TMZ-free solutions. The cytoprotective action of TMZ also reduced interstitial and peritubular inflammation and the numbers of infiltrating mononuclear CD45+ and CD3+ T cells. These results indicate that the tissue damage due to ischemia/reperfusion injury may be prevented, at least in part, by adding TMZ to preservation solutions.

scholarly journals Transplantation-Induced Ischemia-Reperfusion Injury Modulates Antigen Presentation by Donor Renal CD11c+F4/80+ Macrophages through IL-1R8 Regulation

2020 ◽  
Vol 31 (3) ◽  
pp. 517-531 ◽  
Author(s):  
Sistiana Aiello ◽  
Manuel Alfredo Podestà ◽  
Pamela Y. Rodriguez-Ordonez ◽  
Francesca Pezzuto ◽  
Nadia Azzollini ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Antigen Presentation ◽  
Kidney Transplant ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cold Ischemia ◽  
Reversible Ischemia ◽  
Antigen Presenting

BackgroundIn donor kidneys subjected to ischemia-reperfusion injury during kidney transplant, phagocytes coexpressing the F4/80 and CD11c molecules mediate proinflammatory responses and trigger adaptive immunity in transplantation through antigen presentation. After injury, however, resident renal macrophages coexpressing these surface markers acquire a proreparative phenotype, which is pivotal in controlling inflammation and fibrosis. No data are currently available regarding the effects of transplant-induced ischemia-reperfusion injury on the ability of donor-derived resident renal macrophages to act as professional antigen-presenting cells.MethodsWe evaluated the phenotype and function of intragraft CD11c+F4/80+ renal macrophages after cold ischemia. We also assessed the modifications of donor renal macrophages after reversible ischemia-reperfusion injury in a mouse model of congeneic renal transplantation. To investigate the role played by IL-1R8, we conducted in vitro and in vivo studies comparing cells and grafts from wild-type and IL-R8–deficient donors.ResultsCold ischemia and reversible ischemia-reperfusion injury dampened antigen presentation by renal macrophages, skewed their polarization toward the M2 phenotype, and increased surface expression of IL-1R8, diminishing activation mediated by toll-like receptor 4. Ischemic IL-1R8–deficient donor renal macrophages acquired an M1 phenotype, effectively induced IFNγ and IL-17 responses, and failed to orchestrate tissue repair, resulting in severe graft fibrosis and aberrant humoral immune responses.ConclusionsIL-1R8 is a key regulator of donor renal macrophage functions after ischemia-reperfusion injury, crucial to guiding the phenotype and antigen-presenting role of these cells. It may therefore represent an intriguing pathway to explore with respect to modulating responses against autoantigens and alloantigens after kidney transplant.

scholarly journals The effect of neprilysin and renin inhibition on the renal dysfunction following ischemia‐reperfusion injury in the rat

2021 ◽  
Vol 9 (6) ◽  
Author(s):  
Fayez T. Hammad ◽  
Suhail Al‐Salam ◽  
Sarah S. AlZaabi ◽  
Maryam M. Alfalasi ◽  
Awwab F. Hammad ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Renal Dysfunction ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renin Inhibition
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