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J Am Soc Nephrol 11:138-148, 2000
© 2000 American Society of Nephrology

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

THIERRY HAUET*,{dagger}, JEAN-MICHEL GOUJON*, ALAIN VANDEWALLE{ddagger}, HERVE BAUMERT*, LOUIS LACOSTE*, JEAN-PAUL TILLEMENT§, MICHEL EUGENE{dagger} and MICHEL CARRETIER*

* Unité de Chirurgie Expérimentale, Département de génétique animale, Institut National de la Recherche Agronomique (INRA), Le Magneraud, Surgères and GRTMV, Faculté de Médecine, Centre Hospitalo Universitaire, La Milétrie, Poitiers, France
{dagger} Laboratoire de RMN et Explorations Fonctionnelles, Hôpital Saint-Louis, Paris, France
{ddagger} Institut National de la Santé et de la Recherche Médicale, Unité U478, Institut Fédératif de Recherche 02, Faculté de Médecine Xavier Bichat, Paris, France
§ Laboratoire de Pharmacologie, Faculté de Médecine, Paris XII, Créteil, France.

Correspondence to Dr. Thierry Hauet, Unité de Chirurgie Expérimentale, Département de génétique animale, Institut National de la Recherche Agronomique, Le Magneraud, B.P. 52, 17000 Surgères, France. Phone: +33 5 46 68 30 56; Fax: +33 5 46 68 30 87; E-mail: hauet{at}magneraud.inra.fr

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.




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