Objectives: Hepatic ischemia-reperfusion injury and transfusion of red blood cells in liver surgery are wellknown risk factors to induce acute tubular injury. Transfusion of stored red blood cells may affect hepatic ischemia-reperfusion injury-induced acute tubular injury. Here, we hypothesized whether preischemic (due to increased severity of hepatic injury) and postischemic (due to renal uptake of free heme and iron) transfusion of stored red blood cells may potentiate acute tubular injury in rats subjected to hepatic ischemia-reperfusion injury.
Materials and methods: Sprague Dawley rats (n = 24) were divided into 4 groups: sham operation (sham group), hepatic ischemia-reperfusion injury only (injury-only group), red blood cell transfusion before hepatic ischemia-reperfusion injury (preinjury transfusion group), and red blood celltransfusion after hepatic ischemia-reperfusion injury (postinjury transfusion group). Partial hepatic ischemia was induced for 90 minutes, with reperfusion allowed for 12 hours. Hepatic and renal tubular injury markers, renal mRNA levels of oxidant stress markers, and inflammatory markers were assessed. Renal cortex samples were examined under hematoxylin and eosin staining for tubular histopathologic score and immunohistochemical staining forinflammatory cells.
Results: With regard to hepatic and renal tubular injury markers, serum alanine aminotransferase, serum urea nitrogen, and histopathologic scores were increased in the preinjury and postinjury transfusion groups versus injury-only group, with moderate to strong correlation between alanine aminotransferase and tubular injury markers. Renal oxidative stress markers (heme oxygenase-1 and neutrophil gelatinaseassociated lipocalin) were correlated with increased alanine aminotransferase, with upregulation of oxidant stress markers in the preinjury transfusion group versus sham group (all markers), as well as in the injury-only and postinjury transfusion groups (heme oxygenase-1 only). We observed no changes in renal inflammatory responses among the groups.
Conclusions: Preischemic transfusion potentiated acute tubular injury without triggering renal inflammatory responses. Exacerbation of hepatic injury may induce acute tubular injury via renal oxidant stress.