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Abstract: TH-PO143

Effect of Evocalcet on Parathyroid Calcium-Sensing Receptor and Vitamin D Receptor Expressions in Uremic Rats

Session Information

  • CKD-MBD: Targets and Outcomes
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Saito, Tomohiro, Showa Daigaku, Shinagawa-ku, Tokyo, Japan
  • Mizobuchi, Masahide, Showa Daigaku, Shinagawa-ku, Tokyo, Japan
  • Sakai, Mariko, Kyowa Kirin Kabushiki Kaisha, Chiyoda-ku, Tokyo, Japan
  • Kawata, Takehisa, Kyowa Kirin Kabushiki Kaisha, Chiyoda-ku, Tokyo, Japan
  • Kitayama, Tetsuya, Kyowa Kirin Kabushiki Kaisha, Chiyoda-ku, Tokyo, Japan
  • Kato, Tadashi, Showa Daigaku, Shinagawa-ku, Tokyo, Japan
  • Suzuki, Taihei, Showa Daigaku, Shinagawa-ku, Tokyo, Japan
  • Ogata, Hiroaki, Showa Daigaku Yokohama-shi Hokubu Byoin, Yokohama, Kanagawa, Japan
  • Koiwa, Fumihiko, Showa Daigaku Fujigaoka Byoin, Yokohama, Kanagawa, Japan
  • Honda, Hirokazu, Showa Daigaku, Shinagawa-ku, Tokyo, Japan
Background

Little is known about the effect of recently developed calcimimetics evocalcet on the parathyroid calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) expressions.

Methods

We examined the effect of evocalcet and cinacalcet on the CaSR and VDR expressions in 5/6 nephrectomized Sprague-Dawley rats fed a high-phosphate diet for 4 weeks to develop secondary hyperparathyroidism. These rats were divided into groups; baseline control (Nx4W), treated with vehicle (V), evocalcet (E), or cinacalcet (C). After 2 weeks of treatment, blood chemistries and parathyroid tissues were analyzed. CaSR and VDR expression were determined by immunohistochemistry. Normal rats were used as normal control (NC).

Results

The degree of kidney injury and hyperphosphatemia was similar in the uremic groups (Nx4W, V, E, and C). Serum iPTH levels were significantly higher in Nx4W (2424 pg/ml, p<0.01) and V (2098 pg/ml, p<0.01) than in NC (103 pg/ml). This increase was significantly suppressed in E (29 pg/ml, p<0.01) and C (395 pg/ml, p<0.01) compared with V. Serum calcium levels were significantly and equally lower in E (4.7mg/dl, p<0.01) and C (5.7 mg/dl, p<0.01) than in V (8.1 mg/dl). CaSR expression was significantly decreased in Nx4W (16.9 %, p<0.01) and V (16.5 %, p<0.01) compared with NC (45.0 %). The decreased expression was significantly and equally up-regulated in E (46.0 %, p<0.01) and C (40.7 %, p<0.01). A similar trend was observed in VDR expression (62.6% in NC, 16.2 % in Nx4W, 20.2 % in V, 62.2 % in E, and 83.6 % in C).

Conclusion

These results indicate that evocalcet can up-regulate the decreased parathyroid CaSR and VDR expressions in uremic rats, which could contribute to its suppressive effect on PTH.

Funding

  • Commercial Support