Deferoxamine reduces cold-ischemic renal injury in a syngeneic kidney transplant model.
In cell-culture models, addition of deferoxamine (DFO) to University of Wisconsin Solution (UW solution) reduces cold-storage injury. The efficacy of DFO was therefore tested in a kidney transplantation model employing inbred Wistar Furth rats. Donor left kidneys, cold stored for 18 h in UW solution with or without 0.125 mM or 0.625 mM DFO were transplanted to the recipients' left renal fosse. Deferoxamine dose-dependently and significantly increased glomerular filtration rate (GFR) and renal blood flow (RBF), and suppressed renal F2-isoprostanes (vasoactive lipid peroxidation products) and apoptotic and necrotic injury 3 days post-transplantation. In a second set of similar experiments, the remaining native kidneys of the recipient rats were removed on day 7 of transplantation. Transplanted kidneys' function assessed by serum creatinine was 75% higher in the cold-stored transplanted kidneys treated with DFO compared with untreated kidneys. Moreover, the DFO treatment was attended by a significant reduction in apoptotic and necrotic tubular injury. Thus, our consistent findings from two sets of studies in a transplant model suggest that a simple strategy of including DFO in the cold-storage solution reduces cold ischemia-associated renal transplant damage and improves renal function. Our findings have potentially important ramifications for cold preservation of kidneys, and possibly other organs, in clinical transplantation.
Huang
Hong
H
Department of Medicine, University of Mississippi Medical Center, Jackson, USA.
He
Zhi
Z
Roberts
L Jackson
LJ
Salahudeen
Abdulla K
AK
D000818:Animals; D003080:Cold Temperature; D003676:Deferoxamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007511:Ischemia / Q000188:drug therapy*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014185:Transplantation, Isogeneic
D007502:Iron Chelating Agents; D003676:Deferoxamine