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Updated: Oct 10, 2026
The Mouse Isolated Perfused Kidney Technique
Published on: November 17, 2016
Effect of endothelin receptor antagonist (TAK-044) on autotransplanted perfused kidneys in dogs
K Yoshida1, Y Kagebayashi, T Kitauchi
1Division of Hemodialysis Unit, Nara Medical University, Nara, Japan. Kappo@nmu-gw.naramed-u.ac.jp
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.
Insights
The endothelin receptor antagonist TAK-044 improved survival and reduced kidney damage in dogs undergoing kidney autotransplantation. This suggests TAK-044 may prevent acute tubular necrosis following renal transplantation in humans.
Area of Science:
- Nephrology
- Transplantation Immunology
- Pharmacology
Background:
- Endothelin-1 (ET-1) plays a role in renal disease and post-transplant complications.
- TAK-044 is a novel endothelin receptor antagonist blocking ETA and ETB receptors.
- Previous studies showed TAK-044's efficacy in treating acute renal failure in rats.
Purpose of the Study:
- To investigate the therapeutic effect of TAK-044 on autotransplanted kidneys subjected to prolonged perfusion.
- To evaluate the impact of TAK-044 on renal function and survival rates in a canine model.
Main Methods:
- Dogs received either TAK-044 (15 mg/kg/day) or saline subcutaneously for two weeks post-kidney autotransplantation.
- Renal function and survival were monitored.
- Histopathological and immunohistochemical analyses for ET-1 were conducted.
Main Results:
- TAK-044 treatment significantly improved survival rates (5/7 dogs) compared to the control group (2/7 dogs) after 18 hours of kidney perfusion.
- Histological examination revealed amelioration of severe tubular damage in the TAK-044 group.
- Immunohistochemistry confirmed ET-1 presence in tubules of the control group.
Conclusions:
- TAK-044 demonstrates a protective effect against kidney damage in autotransplanted organs.
- The findings suggest TAK-044's potential utility in mitigating acute tubular necrosis after human renal transplantation.
