Apoptosis and treatment of chronic allograft nephropathy with everolimus.
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.
Lutz
Jens
J
Department of Nephrology, Klinikum rechts der Isar, München, Germany.
Zou
Hequn
H
Liu
Shanying
S
Antus
Balazs
B
Heemann
Uwe
U
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002908:Chronic Disease; D000068338:Everolimus; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D016030:Kidney Transplantation; D011183:Postoperative Complications; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use*; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus