Background: Endothelin-1 (ET-1) is involved in some diseases, including renal disease. Recently, the role of ET-1 in postrenal transplantation has been demonstrated in experimental and clinical studies. A new endothelin receptor antagonist, TAK-044, blocks both, ETA and ETB receptors, and was useful in treating acute renal failure in rats. In this study, we evaluated the effect of TAK-044 on autotransplanted kidneys with 18 h of perfusion. Materials and Methods: TAK-044 was injected subcutaneously at 15 mg/kg/day for 2 weeks in one group of dogs, and blood analysis and renal function, were evaluated. A control group was given saline in the same manner as that used for the TAK-044 group. Histopathological examination and immunohistochemistry for ET-1 were performed in the two groups. Results: In the control group, 5 of the 7 dogs died of renal failure within 2 weeks after autotransplantation of the kidney. In the TAK-044 group, 5 of the 7 dogs survived and 2 died of renal failure within the same period. Although the histological changes in the tubules in both groups were severe due to the 18 h of perfusion, TAK-044 ameliorated these changes. Immunohistochemical staining for ET-1 was seen in tubules in the control group. Conclusion: These findings suggest that TAK-044 effectively reduces damage in autotransplanted perfused kidneys in dogs, and may be useful in limiting damage to the kidney by acute tubular necrosis after renal transplantation in humans.

Keywords:
Endothelin receptor antagonist (TAK-044), Autotransplanted kidney, Dog, Immunohistochemistry
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© 2000 S. Karger AG, Basel
2000
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