Attenuation of renal ischemia-reperfusion injury by FR167653 in dogs

Background. Inflammatory cytokines are known to contribute to ischemia-reperfusion injury. We investigated the effect of FR167653 (FR), a suppressor of interleukin-1β and tumor necrosis factor-α, on ischemia-reperfusion injury of the kidney in dogs. Methods. The left kidney was subjected to ischemia for 60 minutes followed by removal of the right kidney. A control group (n = 10) and an FR group (n = 8) were evaluated for tissue blood flow; resistive index, pulsatility index, arterial oxygen pressure, serum creatinine, blood urea nitrogen, aspartate transaminase, and alanine transaminase levels; interleukin-1β messenger RNA expression in the peripheral blood; apoptotic index; and histopathology. Results. The FR group showed lower creatinine, serum urea nitrogen, aspartate transaminase, and alanine transaminase levels (P < .038 each) and lower interleukin-1β mRNA expression and apoptotic index (P < .041 each) than did the control group. Arterial oxygen pressure during the 120 minutes after reperfusion in the FR group decreased but recovered quickly (P = .024). Renal tissue damage in the FR group was less than that in the control group (P = .036). Conclusions. FR ameliorates ischemia-reperfusion injury of the kidney potentially by reduced production of inflammatory cytokines that may contribute to damage to the ischemic kidney and the distant organs. (Surgery 2002;131:654-62.)