A primate model of renal ischemia-reperfusion injury for preclinical evaluation of the antileukocyte function associated antigen 1 monoclonal antibody odulimonab

Purpose: We established a primate model to investigate the effects of the a ntileukocyte function associated antigen 1 (CD 11a) mAb odulimomab (Imtix-S angstad, Lyon, France) for preventing renal ischemia-reperfusion injury. Materials and Methods: We randomly divided 34 Macaca cynomolgus monkeys int o groups 1 and 2, which received a renal autograft after 2 hours of cold is chemia, and groups 3 and 4, which received the autograft. after 24 hours of cold ischemia. Before cold ischemia all harvested kidneys were subjected t o 30 to 45 minutes of warm ischemia. Groups 1 and 3 monkeys were treated wi th an antileukocyte function associated antigen 1 mAb before cold ischemia and then for 3 days, while groups 2 and 4 monkeys received an IgG1 isotype control. In all groups renal function was investigated before warm ischemia and 72 hours after reperfusion. Serum creatinine and the leukocyte count w ere determined daily. Histological studies were done and lactoferrin was me asured in the autotransplanted kidney 72 hours after reperfusion. Results: A decrease in renal function was shown after 2 hours of cold ische mia with tubular necrosis and mild cell infiltration, while after 24 hours of cold ischemia there was severe renal failure with tubular and glomerular necrosis, and leukocyte infiltration. A significant improvement in renal f unction and decrease in kidney lactoferrin content was evident in group 1 c ompared to group 2 at 72 hours, while no significant difference was noted i n groups 3 and 4. No difference in histological patterns was evident in tre ated and untreated animals. Conclusions: This study provides evidence for the validity of this ischemia -reperfusion injury model in primates. The protective effects of antileukoc yte function associated antigen 1 mAb on renal injury was not as dramatic a s in rodent models but a significant improvement in renal function was obse rved in treated animals after 2 hours of cold ischemia.