Renoprotective effects of trimetazidine against ischemia-reperfusion injury and cold storage preservation: a preliminary study.
BACKGROUND
Initial ischemia-reperfusion injury is associated with organ retrieval, storage, and transplantation adversely affects early graft function and influences the development of chronic graft dysfunction. We have recently shown that the protective agent trimetazidine (TMZ) added to preservation solutions: Euro-collins (EC) and University of Wisconsin (UW) was efficient to protect kidneys from ischemia-reperfusion injury in an isolated perfused kidney model. We extended these observations to investigate the role of this drug in the development and progression of organ dysfunction in the autotransplant pig kidney model.


METHODS
Five experimental groups were studied. After 48-hr cold preservation, autotransplantation and immediate controlateral nephrectomy was then performed in group EC (EC+placebo (n=8), EC+TMZ (n=8), UW+placebo (n=7), and (UW+TMZ) (n=7) and compared with control group (uninephrectomized, n=4) during 14 days. Blood and urine samples were collected for the measurement of creatinine and blood urea nitrogen on postoperative days 1, 3, 5, 7, 11, and 14. Histological analysis was performed after reperfusion and at day 14.


RESULTS
Survivals were 100% in group B and D versus 42% in group A and 57% in group C. Urine production occurred earlier after autotransplantation from TMZ preserved kidneys than in placebo preserved groups. Peak creat and blood urea nitrogen was significantly greater in groups B and D than in groups A and C. TMZ was also efficient both to reduce ischemia-reperfusion injury and to decrease cellular infiltration.


CONCLUSIONS
These results support the beneficial effect of TMZ against ischemia-reperfusion injury and its early effects on grafts in the form of delayed graft function and decreased graft survival. In addition, TMZ reduces inflammatory cellular infiltration in the renal parenchyma.
Baumert
H
H
Département de Génétique Animale, Institut National de la Recherche Agronomique, GRTMV EA 2426, Faculté de Médecine, Poitiers, France.
Goujon
J M
JM
Richer
J P
JP
Lacoste
L
L
Tillement
J P
JP
Eugene
M
M
Carretier
M
M
Hauet
T
T
D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D003080:Cold Temperature; D003451:Cryoprotective Agents / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology; D006085:Graft Survival / Q000502:physiology; D006982:Hypertonic Solutions; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation / Q000276:immunology; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology; D011887:Raffinose / Q000494:pharmacology; D015427:Reperfusion Injury / Q000517:prevention & control; D013552:Swine; D014292:Trimetazidine / Q000494:pharmacology*
D003451:Cryoprotective Agents; C037096:Euro-Collins' solution; D006982:Hypertonic Solutions; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D014292:Trimetazidine