title: Atorvastatin donor pretreatment prevents ischemia/reperfusion injury in renal transplantation in rats: possible role for aldose-reductase inhibition.
abstract: BACKGROUND
  The aim of the present study was to evaluate the effect of donor pretreatment with atorvastatin on ischemia/reperfusion (I/R) injury in renal transplantation in rats.
  
  
  METHODS
  Donor rats were pretreated orally with atorvastatin or vehicle 2 days prior to explantation. Kidneys were stored for 24 hr at 4 degrees C in University of Wisconsin solution and transplanted into isogeneic or allogeneic recipients.
  
  
  RESULTS
  Donor treatment with atorvastatin improved initial graft function, reduced renal inflammation, and the number of TUNEL-positive cells in renal tissue after prolonged cold storage and isogeneic transplantation. In the allogeneic transplantation model, donor treatment with atorvastatin reduced renal inflammation in grafts harvested after 5 days, but no improvement of long-term graft survival (24 weeks) could be observed. A genome wide gene expression profile of donor kidneys from atorvastatin treated or vehicle treated rats revealed a fivefold downregulation of aldose reductase in all atorvastatin treated animals (P<0.01). Donor treatment with an aldose-reductase inhibitor improved kidney function and reduced renal inflammation after prolonged cold storage and isogeneic transplantation.
  
  
  CONCLUSIONS
  Our data suggest that downregulation of aldose reductase in renal tissue might underlie the protective effect of donor atorvastatin treatment. Donor pretreatment with a statin or an aldose reductase inhibitor could offer a new treatment strategy to prevent transplantation associated tissue injury.
authors: Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Hospital Mannheim, University of Heidelberg, Mannheim, Germany. uwe.goettmann@med5.ma.uni-heidelberg.de
authors: Uwe
authors: U
authors: Gottmann
authors: Paul T
authors: PT
authors: Brinkkoetter
authors: Simone
authors: S
authors: Hoeger
authors: Katrin
authors: K
authors: Gutermann
authors: Zora Martins
authors: ZM
authors: Coutinho
authors: Tobias
authors: T
authors: Ruf
authors: Song
authors: S
authors: Hui
authors: Zhenzi
authors: Z
authors: Liu
authors: Peter
authors: P
authors: Schnuelle
authors: Fokko J
authors: FJ
authors: van der Woude
authors: Claude
authors: C
authors: Braun
authors: Benito A
authors: BA
authors: Yard
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000069059:Atorvastatin; D020869:Gene Expression Profiling; D006085:Graft Survival; D006538:Heptanoic Acids / Q000008:administration & dosage*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D000449:Aldehyde Reductase