EFFICIENCY OF TRIMETAZIDINE IN RENAL DYSFUNCTION SECONDARY TO COLD ISCHEMIA-REPERFUSION INJURY - A PROPOSED ADDITION TO UNIVERSITY-OF-WISCONSIN SOLUTION

Nonspecific injury in cadaveric renal transplants adversely affects ea rly graft function and influences long-term graft survival after organ transplantation. Trimetazidine (TMZ) has been reported to exert a pro tective action against normothermic ischemia and reperfusion injury in several experimental and clinical studies. In an isolated perfused pi g kidney model, we investigated the effects of TMZ added to University of Wisconsin solution (UW) during 48 or 72 h of cold storage (CS) and the consequence during reperfusion. Under all conditions tested renal perfusate flow rate (PFR), renal functions, and tubular injury marker s were determined during a 120-min perfusion period. Lipid peroxidatio n and histological examination (optical and electron microscopy) were also determined after CS and reperfusion. The addition of TMZ (10(-6) M) to the UW solution improved dramatically the quality of preserved k idneys and consequently the functional recovery during reperfusion. TM Z + UW also significantly had a protecting role against reperfusion in jury and lipid peroxidation when compared to UW alone. These results w ere correlated with both a better preservation of the proximal blush b order membrane and reduced cellular and mitochondrial swelling. These results also suggested that the TMZ-induced renoprotection correlated well with the observed decrease membrane lipid peroxidation. Therefore , trimetazidine may be useful for clinical kidney graft preservation. (C) 1998 Academic Press.