Abstract: PO1563
Long-Term Effect of Novel Morphometric 3D Capsule Device to Constrain Growth in Polycystic Kidney: Comparison Between Wild-Type, Cy/+, and PCK Rat Models
Session Information
- Cystic Kidney Diseases: Emerging Concepts, Biomarkers, and Clinical Trials
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1001 Genetic Diseases of the Kidneys: Cystic
Authors
- Bae, Kyongtae Ty, University of Pittsburgh, Department of Radiology, Pittsburgh, Pennsylvania, United States
- Yoshimura, Aya, Fujita Health University, Education and Research Center of Animal Models for Human Diseases, Toyoake, Japan
- Kumamoto, Kanako, Fujita Health University, Education and Research Center of Animal Models for Human Diseases, Toyoake, Japan
- Kugita, Masanori, Fujita Health University, Education and Research Center of Animal Models for Human Diseases, Toyoake, Japan
- Yamaguchi, Tamio, Suzuka University of Medical Science Faculty of Health Science, Department of Clinical Nutrition, Suzuka, Japan
- Horie, Shigeo, Juntendo University, Faculty of Medicine,Department of Urology, Tokyo, Japan
- Bae, Junu, Ohio State University College of Medicine, Columbus, Ohio, United States
- Nagao, Shizuko, Fujita Health University, Education and Research Center of Animal Models for Human Diseases, Toyoake, Japan
Background
As a potential therapeutic method to halt the progression of polycystic kidney disease, we developed and implanted a computed tomography (CT) image-derived morphometric 3D capsule device to encase a kidney. In this study, the long-term effect of the capsule device on size, function, and histology of polycystic kidneys were assessed using wild-type, Cy/+ and PCK rat models.
Methods
Kidney capsule devices were designed from CT images of rats and surgically implanted on left kidneys, while sham operations performed as controls, in wild-type (n=2), Cy/+ (n=2) and PCK (n=3) rats. After operation, rats were followed to grow. Monthly CT scans were performed and used to measure kidney volume. At the final follow-up, rats were sacrificed and kidney weight, serum BUN and creatinine (Cre) were measured. Histological analyses including cystic area measurement and immunohistochemistry were performed.
Results
In wild-type rats, kidney weights in sham and encapsulated (Enc) rats were similar (Right [R]: 2.2g, Left [L]: 2.1g sham vs. R 2.3g, L 2.2g Enc). In Cy/+ rats survived over 6 months, kidney weights, BUN, and Cre were all lower in Enc rats than those in sham rats (Weight: R 4.7g, L 4.6g sham vs. R 3.6g, L 2.9g Enc (Figure); BUN mg/dL: 113.8 sham vs. 44.9 Enc; Cre mg/dL: 2.06 sham vs. 0.71 Enc). In PCK rats survived over 3 months, kidney weights, BUN, and Cre were all lower in Enc rats than those in sham rats (Weight: R 5.6g, L 6.0g sham vs. R 4.5g, L 3.8g Enc; BUN: 30.6 sham vs. 22.9 Enc; Cre: 0.43 sham vs. 0.36 Enc). Encapsulated kidneys of polycystic rats showed smaller histologic cystic area with reduced cell proliferation and macrophages than unencapsulated kidneys.
Conclusion
Both Cy/+ and PCK rats in long-term follow-ups showed considerable reductions in size of the kidneys that were encapsulated with morphometric 3D capsule devices as well as reduction in BUN and creatinine, demonstrating proof of concept toward a novel potential therapeutic avenue for halting progression of polycystic kidney disease.
Funding
- Government Support - Non-U.S.