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Novel 3D capsule device to restrict kidney volume expansion on polycystic kidney progression: feasibility study in a rat model

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Abstract

Background

Cystogenesis in polycystic kidney disease (PKD) is likely accelerated by various renal insults, including crystal deposition, that activate renal tubule obstruction and dilation. We developed a capsule-based device that can be applied to cystic kidneys to restrict tubular lumen dilatation and cyst expansion.

Methods

Kidney capsule devices were designed from computed tomography images of wild-type and Cy/+ rats. Capsule devices were surgically implanted on kidneys in six surgical sessions over a period of 14 months in 7 wild-type rats of 6.5–8 weeks (3 sham operations, 2 right, 2 left) and 6 Cy/+ rats of 6.5 weeks (2 sham, 3 left, 1 bilateral). After surgery, the rats were followed for 5.4–12.4 weeks’ growth and sacrificed to retrieve the kidneys. During the follow-up, serum creatinine was measured and retrieved kidneys were weighed. Histological analysis including cystic area measurement and immunohistochemistry was performed.

Results

Morphometric capsule devices were configured and developed by an image processing technique and produced using a 3D printer. Encapsulated Cy/+ kidneys (n = 5; mean weight 3.64 g) were consistently smaller in size (by 21–36%; p < 0.001) than unencapsulated Cy/+ kidneys (n = 7; mean weight 5.52 g). Encapsulated Cy/+ kidneys (mean %cyst area: 29.4%) showed smaller histological cystic area (by 28–58%; p < 0.001) than unencapsulated Cy/+ kidneys (mean %cyst area 48.6%). Cell proliferation and macrophages were also markedly reduced in encapsulated Cy/+ kidneys, compared to unencapsulated Cy/+ kidneys.

Conclusions

We report a pilot feasibility study for the application of a novel morphometric 3D capsule device to the Cy/+ rat model showing restricted kidney volume expansion on polycystic kidney disease progression.

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Acknowledgements

We thank Seongho Park, MD (Asan Medical Center, Korea) for support with statistical analysis. This work was supported by grants from the Fujita Health University (PI, S.N.).

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Author notes

  1. Kyongtae T. Bae, Kanako Kumamoto, and Aya Yoshimura contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, University of Pittsburgh School of Medicine, 300 Halket St. Suite C-316, Pittsburgh, PA, 15213, USA

    Kyongtae T. Bae

  2. Education and Research Facility of Animal Models for Human Diseases, Center for Research Promotion and Support, Fujita Health University, 1-98 Dengakugakubo Kutsukake, Toyoke, Aichi, 470-1192, Japan

    Kanako Kumamoto, Aya Yoshimura, Masanori Kugita & Shizuko Nagao

  3. Department of Urology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan

    Shigeo Horie

  4. Department of Clinical Nutrition, Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie, Japan

    Tamio Yamaguchi

  5. Ohio State University College of Medicine, Columbus, OH, USA

    Junu T. Bae

Authors
  1. Kyongtae T. Bae
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  2. Kanako Kumamoto
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  3. Aya Yoshimura
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  4. Masanori Kugita
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  5. Shigeo Horie
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  6. Tamio Yamaguchi
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  7. Junu T. Bae
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  8. Shizuko Nagao
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Contributions

K.T.B., S.H., T.Y., and S.N. formulated the ideas and planned the experiments. K.T.B. designed and developed the 3D kidney capsule devices. K.K. and A.Y. performed the animal experiments. K.K., A.Y., and M.K. analyzed renal function and histology. K.T.B., K.K., A.Y., T.Y., and S.N. analyzed the data and wrote the manuscript. S.H. and J.T.B edited the manuscript. All the authors reviewed and accepted the contents of the article. K.T.B., K.K., and A.Y. equally contributed to this manuscript.

Corresponding authors

Correspondence to Kyongtae T. Bae or Shizuko Nagao.

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Conflict of interest

K.T.B. is a consultant to Kadmon, Otsuka, and Sanofi and submitted a provisional patent application. K.K., A.Y., M.K., S.H., T.Y., J.T.B, and S.N. have no conflicts of interest to declare.

Ethical approval

This study was approved by the Fujita Health University Animal Care and Use Committee and followed the ARRIVE guidelines.

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Bae, K.T., Kumamoto, K., Yoshimura, A. et al. Novel 3D capsule device to restrict kidney volume expansion on polycystic kidney progression: feasibility study in a rat model. J Nephrol 35, 1033–1040 (2022). https://doi.org/10.1007/s40620-021-01160-5

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  • DOI: https://doi.org/10.1007/s40620-021-01160-5

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