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.
Original language | English (US) |
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Pages (from-to) | 1531-1537 |
Number of pages | 7 |
Journal | American Journal of Transplantation |
Volume | 3 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2003 |
Keywords
- Cold ischemia
- Cold storage
- DFO
- Deferoxamine
- F2-isoprostanes
- Iron
- Iron chelator
- Kidneys
- Transplantation
ASJC Scopus subject areas
- Immunology and Allergy
- Transplantation
- Pharmacology (medical)