Deferoxamine reduces cold-ischemic renal injury in a syngeneic kidney transplant model

Am J Transplant. 2003 Dec;3(12):1531-7. doi: 10.1046/j.1600-6135.2003.00264.x.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cold Temperature
  • Deferoxamine / pharmacology*
  • Dose-Response Relationship, Drug
  • Iron Chelating Agents / pharmacology*
  • Ischemia / drug therapy*
  • Kidney / blood supply
  • Kidney / drug effects*
  • Kidney / pathology
  • Kidney Transplantation*
  • Male
  • Rats
  • Rats, Wistar
  • Transplantation, Isogeneic*

Substances

  • Iron Chelating Agents
  • Deferoxamine