The role of oxygen free radicals in mediating the reperfusion injury of cold-preserved ischemic kidneys

Isamu Koyama, Gregory B. Bulkley, G. Melville Williams, Michael J. Im

Research output: Contribution to journalArticle

Abstract

We evaluated the hypothesis that postischemic renal failure is caused primarily at reperfusion by oxygen-derived free radicals in a swine model designed to realistically mimick human cadaveric renal transplantation. Both kidneys were removed, flushed with Euro-Collins solution, stored 24 hr at 4°C, and then transplanted to a second pig. Experiments were paired, each pig receiving one treated and one control kidney. All pigs received the optimal conventional regimen of hydration, phenoxybenzamine, furosemide, and mannitol to allow assessment of free radical treatment superimposed thereupon. Two days later creatinine clearance (CCr) was measured from each kidney via separate ureterostomies. Untreated kidneys developed severe functional impairment, CCR falling from a normal level of 25.5± 6.3 ml/min (n=8) to 7.7±0.9 ml/min (n=14, PCR=15.9±1.7 ml/min, n=18, PCR=8.0±1.1 ml/min, n=4) or 2 mg (CCR=7.7± 0.9, n=5), and no greater benefit from 100 mg (CCR=16.1±2.1 ml/min, n=3, PCR=18.2±1.8; n=11, PCR=22.1±0.6 ml/min). Consequently, under these conditions the ablation of free radical generation with allopurinol provided no significant benefit. These findings suggest that after a critical period of cold ischemic preservation, metabolic changes take place within the kidney that lead to free radical generation and consequent tissue injury upon reperfusion, despite optimal preservation by conventional methods. This damage can be prevented by simple nontoxic measures—which, therefore, show great promise for use in the prevention of early renal failure following cadaveric renal transplantation.

Original languageEnglish (US)
Pages (from-to)590-595
Number of pages6
JournalTransplantation
Volume40
Issue number6
StatePublished - 1985

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Reperfusion Injury
Free Radicals
Reactive Oxygen Species
Kidney
Swine
Polymerase Chain Reaction
Kidney Transplantation
Renal Insufficiency
Ureterostomy
Phenoxybenzamine
Allopurinol
Furosemide
Mannitol
Reperfusion
Creatinine
Oxygen
Therapeutics

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Koyama, I., Bulkley, G. B., Williams, G. M., & Im, M. J. (1985). The role of oxygen free radicals in mediating the reperfusion injury of cold-preserved ischemic kidneys. Transplantation, 40(6), 590-595.

The role of oxygen free radicals in mediating the reperfusion injury of cold-preserved ischemic kidneys. / Koyama, Isamu; Bulkley, Gregory B.; Williams, G. Melville; Im, Michael J.

In: Transplantation, Vol. 40, No. 6, 1985, p. 590-595.

Research output: Contribution to journalArticle

Koyama, I, Bulkley, GB, Williams, GM & Im, MJ 1985, 'The role of oxygen free radicals in mediating the reperfusion injury of cold-preserved ischemic kidneys', Transplantation, vol. 40, no. 6, pp. 590-595.
Koyama, Isamu ; Bulkley, Gregory B. ; Williams, G. Melville ; Im, Michael J. / The role of oxygen free radicals in mediating the reperfusion injury of cold-preserved ischemic kidneys. In: Transplantation. 1985 ; Vol. 40, No. 6. pp. 590-595.
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