Kidney Week

Abstract: FR-PO576

Urinary Exosome Analysis in a Case of Licorice-Induced Pseudoaldosteronism

Session Information

• Trainee Case Reports - III
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Reports

• 902 Fluid and Electrolytes: Clinical

Authors

• Asakawa, Shinichiro, Teikyo University School of Medicine , Tokyo, Japan

Shinichiro Asakawa,

• Yamazaki, Osamu, Teikyo University School of Medicine , Tokyo, Japan

Osamu Yamazaki,

• Hayama, Yuto, Teikyo University School of Medicine , Tokyo, Japan

Yuto Hayama,

• Yamanaka, Masaki, Teikyo University School of Medicine , Tokyo, Japan

Masaki Yamanaka,

• Kuribayashi-Okuma, Emiko, Teikyo University School of Medicine , Tokyo, Japan

Emiko Kuribayashi-Okuma,

• Fujigaki, Yoshihide, Teikyo University School of Medicine, Department of Internal Medicine, Tokyo, Japan

Yoshihide Fujigaki,

• Shibata, Shigeru, Teikyo University School of Medicine , Tokyo, Japan

Shigeru Shibata,

Group or Team Name

• Teikyo University School of Medicine

Introduction

Excessive licorice intake can cause a syndrome mimicking hypermineralocorticoidism. Glycyrrhizin, the active metabolite of licorice, inhibits 11bHSD2 that converts cortisol to inactive cortisone, resulting in epithelial Na⁺ channel (ENaC) activation in principal cells. However, the contributions of other Na and Cl transporters including Na-Cl cotransporter (NCC) in distal convoluted tubules and the Cl/HCO₃ exchanger pendrin in intercalated cells remain unknown.

Case Description

A 74-year-old woman with type 2 diabetes was referred for muscle weakness, leg edema, and polyuria. She reported that she had been taking herbal medicine containing licorice (6 g/day). Her BP was 162/78 mmHg and work up revealed severe hypokalemia (1.9 mEq/L), mild hypernatremia (147 mEq/L), and metabolic alkalosis (pH 7.513, and HCO₃ 43.2 mmol/L). Urinary potassium level was 84.0 mEq/gCr, indicating the urinary potassium loss. Serum magnesium level was 1.9 mg/dL. Her serum aldosterone level was below the detection limit (< 10 pg/mL) with low plasma renin activity (0.3 ng/mL/hour). Serum cortisol and adrenocorticotropic hormone were normal. Abdominal CT scan and Doppler ultrasound of renal arteries revealed no abnormality. She stopped taking licorice and received KCl 40 mmol of DIV and 24 mmol oral in first 24 hrs. However, hypokalemia persisted, and the patient received 25mg of spironolactone orally from day 3. On day 10, serum potassium returned to normal, and was discharged on day 13. To address the contribution of Na and Cl transport mechanisms in the distal nephron, we isolated exosomes from pre- and post-treatment urine samples.Comparison of the pre- and post-treatment samples revealed that active, cleaved form of ENaCγ was markedly increased, whereas uncleaved form was undetectable in the pre-treatment sample, consistent with the increased activity of ENaC. Of note, both pendrin and NCC levels were profoundly increased in the pre-treatment sample, and were reduced after the treatment. In contrast, NKCC2 levels were lower in the pre-treatment sample than in the post-treatment sample.

Discussion

These data indicate that not only ENaC but NCC and pendrin are involved in licorice-induced fluid and electrolyte abnormalities.