BACKGROUND: Chronic allograft nephropathy (CAN) is responsible for most cases of late kidney allograft loss. However, no effective treatment is available so far. Everolimus (RAD) (40-O [2-hydroxyethyl] rapamycin) is a new immunosuppressive agent with antiproliferative and apoptosis-enhancing effects. We asked whether everolimus can ameliorate CAN even at advanced stages, whether everolimus treatment affects the level of growth factor mRNA, and whether everolimus treatment affects the number of apoptotic cells in the graft. METHODS: We transplanted kidneys from Fisher rats into Lewis rats and treated recipients with everolimus over different time periods. Grafts were analyzed 20 or 28 weeks after transplantation. RESULTS: Everolimus delayed the progression of CAN when started at an early stage. Surprisingly, everolimus even ameliorated CAN when initiated at an advanced stage. Interestingly, apoptosis was more prevalent in treated animals, particularly in those with delayed treatment as compared with controls. CONCLUSIONS: Everolimus ameliorates CAN as a result of antiproliferative or apoptosis-enhancing effects.
BACKGROUND:Chronic allograft nephropathy (CAN) is responsible for most cases of late kidney allograft loss. However, no effective treatment is available so far. Everolimus (RAD) (40-O [2-hydroxyethyl] rapamycin) is a new immunosuppressive agent with antiproliferative and apoptosis-enhancing effects. We asked whether everolimus can ameliorate CAN even at advanced stages, whether everolimus treatment affects the level of growth factor mRNA, and whether everolimus treatment affects the number of apoptotic cells in the graft. METHODS: We transplanted kidneys from Fisher rats into Lewis rats and treated recipients with everolimus over different time periods. Grafts were analyzed 20 or 28 weeks after transplantation. RESULTS:Everolimus delayed the progression of CAN when started at an early stage. Surprisingly, everolimus even ameliorated CAN when initiated at an advanced stage. Interestingly, apoptosis was more prevalent in treated animals, particularly in those with delayed treatment as compared with controls. CONCLUSIONS:Everolimus ameliorates CAN as a result of antiproliferative or apoptosis-enhancing effects.