Experimental study of FR167653 in simultaneous pancreas and kidney transplantation from non-heart-beating donor

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Background. Inflammatory cytokines are known to contribute to ischemia-reperfusion (LIR) injury. We investigated the effect of FR167653 (FR), a suppressor of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, on I/R 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, pulsatilitv_index arterial oxygen pressure (PaO_2), serum creatinine, blood urea nitrogen (BUN), aspartate transaminase (AST), and alanine transaminase (ALT) levels ; IL-1β mRNA expression in the peripheral blood ; apoptotic index ; and histopathology.Results. The FR group showed lower creatinine, BUN, AST, and ALT levels (p<0.038 each) : and lower IL-1β mRNA expression and apoptotic index (p<0.041 each) than did the control group. PaO_2 during 120 minutes after reperfusion in the FR group dropped but recovered quickly (p=0.024). Renal tissue damage in the FR group was less than that in the control group (p=0.036).Conclusions. FR ameliorates I/R injury of the kidney potentially via reduced production of inflammatory cytokines that may contribute to damage to the ischeniic kidney and the distant organs.