Abstract | BACKGROUND: METHODS: Kidneys were perfused ex situ with 2 ml of Euro-Collins solution without or with IP-9125 and exposed to 30-min cold (4 degrees C storage time) and 30-min warm (anastomosis time) ischemia. Kidneys were then transplanted to syngeneic nephrectomized recipients. RESULTS: Within 24 hr after transplantation, the glomerular filtration rate values were reduced by almost 60% to 0.49+/-0.14 ml/min from 1.20+/-0.27 ml/min in normal kidneys (P<0.001). Kidney perfusion with 10 mg of either IP-12140 (0.41+/-0.07 ml/min) or IP-13944 (0.47+/-0.07 ml/min) control oligo was ineffective. In contrast, perfusion with 10 mg of IP-9125 significantly improved kidney function (0.8+/-0.18 ml/min; P<0.005), whereas the lower doses of 2 mg (0.47+/-0.13 ml/min; NS) or 4 mg (0.54+/-0.04 ml/min; NS) had no significant effect. The glomerular filtration rate results were confirmed by measurements of blood creatinine (CR) levels at 24 hr after grafting: untreated recipients had a twofold higher CR value (0.70+/-0.14 mg/dl) compared with normal controls (0.65+/-0.07 mg/dl; P<0.001). Although perfusion with 10 mg of control IP-12140 (0.80+/-0.14 mg/dl) or IP-13944 (0.65+/-0.07 mg/dl) did not affect CR levels, perfusion with 10 mg of IP-9125 (0.45+/-0.07 mg/dl) lowered CR levels. The Western blots or reverse transcription-polymerase chain reaction experiments performed in kidney transplants within 24 hr after grafting showed that 10 mg of IP-9125 (but not control IP-12140) reduced the expression of ICAM-1 protein and ICAM-1 mRNA, respectively. CONCLUSIONS:
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Authors | W Chen, C F Bennett, M E Wang, D Dragun, L Tian, K Stecker, J H Clark, B D Kahan, S M Stepkowski |
Journal | Transplantation
(Transplantation)
Vol. 68
Issue 6
Pg. 880-7
(Sep 27 1999)
ISSN: 0041-1337 [Print] United States |
PMID | 10515390
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Oligodeoxyribonucleotides, Antisense
- Intercellular Adhesion Molecule-1
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Topics |
- Animals
- Female
- Glomerular Filtration Rate
(drug effects)
- Immunohistochemistry
- Intercellular Adhesion Molecule-1
(genetics)
- Kidney
(blood supply, physiology)
- Kidney Transplantation
- Macaca fascicularis
- Male
- Oligodeoxyribonucleotides, Antisense
(therapeutic use)
- Perfusion
- Rats
- Rats, Inbred BUF
- Rats, Sprague-Dawley
- Reperfusion Injury
(prevention & control)
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