Renoprotective effects of trimetazidine against ischemia-reperfusion injury and cold storage preservation: A preliminary study

Background Initial ischemia-reperfusion injury is associated with organ ret rieval, storage, and transplantation adversely affects early graft function and influences the development of chronic graft dysfunction, We have recen tly shown that the protective agent trimetazidine (TMZ) added to preservati on solutions: Euro-collins (EC) and University of Wisconsin (UW) was effici ent to protect kidneys from ischemia-reperfusion injury in an isolated perf used kidney model. We extended these observations to investigate the role o f 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 preservati on, autotransplantation and immediate controlateral nephrectomy was then pe rformed 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) dur ing 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, an d 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 fr om TMZ preserved kidneys than in placebo preserved groups. Peak creat and b lood urea nitrogen was significantly greater in groups B and D than in grou ps A and C, TMZ was also efficient both to reduce ischemia-reperfusion inju ry and to decrease cellular infiltration, Conclusion. These results support the beneficial effect of TMZ against isch emia-reperfusion injury and its early effects on grafts in the form of dela yed graft function and decreased graft survival, In addition, TMZ reduces i nflammatory cellular infiltration in the renal parenchyma.