New strategy for nocturnal polyuria: Aiming for urine absorption through sensory C fibers in the bladder

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18607
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: University of Fukui
• Principal Investigator: OE HIDEKI 福井大学, 学術研究院医学系部門(附属病院部), 医員 (70760510)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 夜間頻尿 / アクアポリン / 抗コリン薬

Outline of Final Research Achievements

Nocturia is the most common symptom among patients with lower urinary tract symptoms in Japan. Anticholinergic drugs for the treatment of overactive bladder are also effective for nocturia, but among them, imidafenacin, a short-acting anticholinergic drug, was compared with the nocturia group in the sub-analysis of the phase 3 study. It was suggested that the amount could be significantly reduced. Therefore, in order to elucidate the mechanism by which anticholinergic drugs reduce urine output, we conducted animal experiments using rats as well. As a result, it was found that imidafenacin, atheropine, tolterodine, and desmopressin suppress urine production in a dose-dependent manner by increasing cAMP and transferring the AQP2 molecule to luminal measurement in the rat renal cortex.

Free Research Field

排尿

Academic Significance and Societal Importance of the Research Achievements

本邦の下部尿路症状を有する患者の中で夜間頻尿は最も多い症状であり、日中の眠気をもたらしADLを低下させる。短時間作用型抗コリン薬であるimidafenacinが尿量を減少させることはこれまでも報告があったがその機序は不明であった。本研究により抗コリン薬が尿量を減少させるのは腎皮質におけるcAMP増加とAQP2分子の集合管管腔側への移動によることが判明した。本研究の結果は今後の夜間頻尿治療に対する新薬開発や新たな治療戦略を考える上で役立つ研究成果であったと考える。