This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features! Clipboard, Search History, and several other advanced features are temporarily unavailable. 1 Department of Organ Transplant and Endocrinological Surgery, Kyoto Prefectural University of Medicine, Kyoto 602, Japan. 1 Department of Organ Transplant and Endocrinological Surgery, Kyoto Prefectural University of Medicine, Kyoto 602, Japan. Tissue factor (TF) is a membrane-bound glycoprotein that is the primary cellular initiator of the blood clotting cascade and its expression is induced on macrophages and endothelial cells during the inflammatory or immune response. Tissue factor pathway inhibitor (TFPI) regulates the extrinsic pathway of blood coagulation through its ability to inhibit tissue factor activity. We studied the role of TF in the kidney following warm ischemic reperfusion and studied the effect of TFPI in vivo. After laparotomy of Lewis rats, the right kidney was harvested and left renal artery and vein were clamped. The kidney was reperfused after 60, 120, and 180 min of ischemia. Rats were sacrificed at 0, 1.5, 5, 12, and 24 h after reperfusion with or without TFPI treatment, and the kidney was harvested. Blood samples were collected at 0, 5, 12, and 24 h after reperfusion from the abdominal aorta. Blood urea nitrogen and kalium were monitored. TF expression was also studied by immunohistochemical staining with a monoclonal antibody (HTF-K108). Histologically, the necroses of the tubular epithelial cells were observed 1.5 h after reperfusion. Immunohistochemically, TF staining was positive on the glomerular endothelial cells and stimulated monocytes but negative on the tubular epithelial cells. The necrotic area extended and encompassed almost all of the ischemic kidney by 12 h after reperfusion. TF was stained on the glomerular base membrane, the glomerular endothelial cells, and the stimulated monocytes but was not evident on the necrotic tubular epithelial cells. Fibrinogen was also observed in the glomerular endothelial cells at 5-12 h after reperfusion, while it was slight in normal tissue. With TFPI treatment, the necrotic area was narrow and TF was slightly stained on the endothelial cells. These results suggest that TF plays an important role in the development of renal injury after ischemia and reperfusion. The microcirculatory incompetence due to microthrombus might cause the formation and development of the necrosis. These results also suggest that TFPI plays a key role in modulating tissue factor-dependent blood coagulation, therefore TFPI is a strong medication for prevention of ischemic reperfusion injury.