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Embryonic kidney function in a chronic renal failure model in rodents

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Abstract

Background

Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney.

Methods

Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter.

Results

We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder.

Conclusion

The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

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Acknowledgments

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. We thank Dr. Eiji Kobayashi for microsurgical techniques.

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Authors and Affiliations

  1. Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

    Shuichiro Yamanaka, Susumu Tajiri, Shinya Yokote, Kei Matsumoto & Takashi Yokoo

  2. Department of Urology, St. Marianna University School of Medicine, Kanagawa, Japan

    Eisuke Fujimoto, Yuichi Katsuoka & Tatsuya Chikaraishi

  3. Division of Regenerative Medicine, The Jikei University School of Medicine, Tokyo, Japan

    Eisuke Fujimoto, Shuichiro Yamanaka, Sho Kurihara, Susumu Tajiri, Luna Izuhara, Yuichi Katsuoka & Hirotaka James Okano

  4. Department of Organ Fabrication, Keio University School of Medicine, Tokyo, Japan

    Eiji Kobayashi

  5. Department of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan

    Sho Kurihara

Authors
  1. Eisuke Fujimoto
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  2. Shuichiro Yamanaka
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  3. Sho Kurihara
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  4. Susumu Tajiri
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  5. Luna Izuhara
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  6. Yuichi Katsuoka
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  7. Shinya Yokote
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  8. Kei Matsumoto
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  9. Eiji Kobayashi
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  10. Hirotaka James Okano
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  11. Tatsuya Chikaraishi
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  12. Takashi Yokoo
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Corresponding author

Correspondence to Takashi Yokoo.

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Conflict of interest

None declared.

Ethical considerations

Animal experiments were carried out in accordance with the guidelines set by Jikei University School of Medicine. The protocol was approved by the Experimental Animal Committee of Jikei University (Permit Number: 2015-032) and conformed to the Guidelines for the Proper Conduct of Animal Experiments of the Science Council of Japan (2006), which adhered to the principles of the 3Rs ARRIVE Guidelines. All efforts were made to minimize animal suffering. Specimens from humans were not used.

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Fujimoto, E., Yamanaka, S., Kurihara, S. et al. Embryonic kidney function in a chronic renal failure model in rodents. Clin Exp Nephrol 21, 579–588 (2017). https://doi.org/10.1007/s10157-016-1337-x

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  • DOI: https://doi.org/10.1007/s10157-016-1337-x

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