title: Apoptosis and treatment of chronic allograft nephropathy with everolimus.
abstract: 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.
authors.affiliation: Department of Nephrology, Klinikum rechts der Isar, München, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Lutz
authors.forename: Hequn
authors.initials: H
authors.lastname: Zou
authors.forename: Shanying
authors.initials: S
authors.lastname: Liu
authors.forename: Balazs
authors.initials: B
authors.lastname: Antus
authors.forename: Uwe
authors.initials: U
authors.lastname: Heemann
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus