Protective effects of reducing renal ischemia-reperfusion injury during renal hilar clamping: Use of allopurinol as a nephroprotective agent

Objective: To investigate the relationship between renal ischemia injury and concentrations of 8-isoprostane in a rat kidney model during renal hilar clamping and their correlation with the administration of allopurinol before clamping. Materials and Methods: Reperfusion injury occurs after the reintroduction of blood flow after a prolonged period of ischemia. Thought to be due to oxygen free radicals released by the endothelial, mitochondrial, and parenchymal cells, this process leads to a cascade of events whereby infiltrative leukocytes generate cytokines and reactive oxygen species. The present study was performed in 2 parts. Our primary objective was to first develop a method of quantitating the renal damage using a prostaglandin compound formed in vivo, specifically isoprostane. After the development of this animal model of quantitating renal injury, our second objective was to apply this model and investigate allopurinol's nephroprotective abilities. A microdialysis probe was inserted into the renal parenchyma of rats to allow continuous dialysis and collection of the effluent for isoprostane levels. After clamping of the renal vessels to induce ischemia, the interstitial effluent from the probe was collected and subsequently analyzed for 8-isoprostane levels with and without allopurinol pretreatment. Results: Clamping of the renal hilum in this rat model significantly increased 8-isoprostane levels. After 60 minutes of clamp time, the largest absolute increase in 8-isoprostane levels resulted, representing a 3.2-fold increase from baseline. However, the rats that had been pretreated with allopurinol demonstrated significantly less isoprostane levels, to baseline levels. Conclusion: Allopurinol has demonstrated significant benefits by reducing reperfusion injury in rat kidneys, as demonstrated by the use of 8-isoprostane as a tool for the real-time measurement of ischemic injury.