Atorvastatin donor pretreatment prevents ischemia/reperfusion injury in renal transplantation in rats: possible role for aldose-reductase inhibition.
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.
Gottmann
Uwe
U
Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Hospital Mannheim, University of Heidelberg, Mannheim, Germany. uwe.goettmann@med5.ma.uni-heidelberg.de
Brinkkoetter
Paul T
PT
Hoeger
Simone
S
Gutermann
Katrin
K
Coutinho
Zora Martins
ZM
Ruf
Tobias
T
Hui
Song
S
Liu
Zhenzi
Z
Schnuelle
Peter
P
van der Woude
Fokko J
FJ
Braun
Claude
C
Yard
Benito A
BA
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*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D000449:Aldehyde Reductase