Oxygen free radicals damage kidneys and accumulate during the period of preservation prior to transplantation. We hypothesized that a perfusate containing either an oxygen free radical scavenger such as ceruloplasmin, or an iron-chelating agent such as deferoxamine, would improve kidney preservation. Thirty-eight mongrel dogs underwent autotransplantation of the left kidney after 30 min of warm ischemia and 48 hr of machine perfusion (MOX-100, Water Instruments, Rochester, MN) at 5°C and pH of 7.4. The right kidney was removed at the time of autotransplantation. Four blind code-labeled preservation solutions were tested. SGF-I was used for the control group (Group 1, n = 13), and the remaining animals were transplanted with kidneys preserved with one of three solutions modified from the basic SGF-I solution: Group 2, SGF-I plus deferoxamine (656 mg/liter), n = 8; Group 3, SGF-I ceruloplasmin enriched (72 mg/dl), n = 8; and Group 4, SGF-I ceruloplasmin reduced (3.4 mg/dl), n = 9. Serum creatinine levels were measured daily for 2 weeks and survival curves for each of the four groups were estimated by the Kaplan-Meier method. Peak mean serum creatinine levels ± standard errors in Groups 1 through 4 were 12.6 ± 1.97, 7.8 ± 0.90, 7.1 ± 1.26, and 8.2 ± 1.09, respectively. Repeated measures analysis of variance showed statistically significant differences between the groups with respect to their serum creatinine profiles (Wald's test χ2 with 3 df = 22.39, P value < 0.001). The significant differences in serum creatinine profiles were due to the consistently higher daily average values for Group 1 as compared with the other three groups. Survival rates 2 weeks after transplant were 31, 100, 63, and 67% for Groups 1 to 4, respectively. Comparison of the survival curves using the log-rank test showed statistically significant differences between the groups (χ2 with 3 df = 9.42, P value = 0.024). We conclude that deferoxamine and ceruloplasmin reduce the ischemia reperfusion injury that occurs after revascularization of renal transplants and may be useful for clinical kidney graft preservation.
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