Kidney Week

Abstract: PO1840

Characterization of Pendrin in Urinary Extracellular Vesicles in a Rat Model of Aldosterone Excess and in Human Primary Aldosteronism

Session Information

• Hypertension and CVD: Mechanisms
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1403 Hypertension and CVD: Mechanisms

Authors

• Ochiai, Fumika, Teikyo Daigaku Igakubu Daigakuin Igaku Kenkyuka Naikagaku, Itabashi-ku, Tokyo, Japan

Fumika Ochiai, DrMed

• Kuribayashi-Okuma, Emiko, Teikyo Daigaku Igakubu Daigakuin Igaku Kenkyuka Naikagaku, Itabashi-ku, Tokyo, Japan

Emiko Kuribayashi-Okuma,

• Tsurutani, Yuya, Yokohama Rosai Byoin, Yokohama, Kanagawa, Japan

Yuya Tsurutani,

• Ishizawa, Kenichi, Teikyo Daigaku Igakubu Daigakuin Igaku Kenkyuka Naikagaku, Itabashi-ku, Tokyo, Japan

Kenichi Ishizawa,

• Kawagoe, Mika, Teikyo Daigaku Igakubu Daigakuin Igaku Kenkyuka Naikagaku, Itabashi-ku, Tokyo, Japan

Mika Kawagoe,

• Tomomitsu, Yoshihiro, Teikyo Daigaku Igakubu Daigakuin Igaku Kenkyuka Naikagaku, Itabashi-ku, Tokyo, Japan

Yoshihiro Tomomitsu,

• Hirohama, Daigoro, Teikyo Daigaku Igakubu Daigakuin Igaku Kenkyuka Naikagaku, Itabashi-ku, Tokyo, Japan

Daigoro Hirohama,

• Arai, Shigeyuki, Teikyo Daigaku Igakubu Daigakuin Igaku Kenkyuka Naikagaku, Itabashi-ku, Tokyo, Japan

Shigeyuki Arai,

• Yamazaki, Osamu, Teikyo Daigaku Igakubu Daigakuin Igaku Kenkyuka Naikagaku, Itabashi-ku, Tokyo, Japan

Osamu Yamazaki,

• Tamura, Yoshifuru, Teikyo Daigaku Igakubu Daigakuin Igaku Kenkyuka Naikagaku, Itabashi-ku, Tokyo, Japan

Yoshifuru Tamura,

• Fujigaki, Yoshihide, Teikyo Daigaku Igakubu Daigakuin Igaku Kenkyuka Naikagaku, Itabashi-ku, Tokyo, Japan

Yoshihide Fujigaki,

• Nishikawa, Tetsuo, Teikyo Daigaku Igakubu Daigakuin Igaku Kenkyuka Naikagaku, Itabashi-ku, Tokyo, Japan

Tetsuo Nishikawa,

• Shibata, Shigeru, Teikyo Daigaku Igakubu Daigakuin Igaku Kenkyuka Naikagaku, Itabashi-ku, Tokyo, Japan

Shigeru Shibata,

Background

Pendrin is a Cl/HCO₃ exchanger selectively present in the intercalated cells of the kidney. Although experimental studies demonstrated that pendrin is involved in the fluid volume regulation and acid/base balance, its role in human hypertension is not fully understood. Here, we investigated the changes in pendrin levels in urinary extracellular vesicles (uEVs) isolated from patients with primary aldosteronism (PA) and in a rat model of PA.

Methods

This study included 30 patients who were diagnosed as having PA in Yokohama Rosai Hospital or in Teikyo University Hospital. The protocol was approved by the institutional review board. In animal experiments, SD rats received continuous infusion of aldosterone after uninephrectomy. Isolation of uEV was performed by the ultracentrifugation method in accordance with the previous report (Fernandez-Llama et al. KI 2010).

Results

Western blot analysis revealed that pendrin is detected in dimeric and monomeric forms in uEVs in humans and in rats. In aldosterone-infused rats, pendrin levels in uEVs were highly correlated with the pendrin abundance in the kidney. We also found significant correlation between abundance in uEVs and that in the kidney for Na-Cl cotransporter and epithelial Na channel in this model. In PA patients, pendrin levels in uEVs were reduced by 49% from the baseline by adrenalectomy or pharmacological MR blockade.Correlation analysis revealed that the magnitude of pendrin reduction after treatment significantly correlated with the baseline aldosterone-renin ratio (ARR), and tended to inversely correlate with serum K⁺ levels. Furthermore, a cross-sectional analysis in PA patients confirmed a significant correlation between ARR and pendrin levels in uEVs.

Conclusion

These data are consistent with experimental studies demonstrating the role of pendrin in aldosterone-induced hypertension, and suggest that pendrin analysis in uEVs may also be useful to understand the pathophysiology of human hypertension.