本研究利用韓國全國健保資料庫進行大型世代研究，分析使用β3 腎上腺素受體促效劑（以 mirabegron 為代表）與腎臟癌風險的關聯。研究共納入約 142 萬名膀胱過動症的患者，其中 3229人在接受治療後發生腎臟癌。結果顯示，使用mirabegron的患者腎臟癌發生率較高，為每 1000人年0.7，相較於使用抗膽鹼藥物者的0.5。在單一醫學中心的臨床資料驗證分析中亦得到一致結果，mirabegron 組的腎癌發生率（1.8%）明顯高於抗膽鹼藥物組（0.7%）。整體而言，β3受體促效劑的使用與較高的腎癌風險相關。本研究的優點在於樣本數龐大、追蹤時間長，並搭配臨床資料進行驗證分析，提高結果的可信度。然而，研究設計屬於觀察性世代研究，無法證實因果關係，仍可能受到殘餘混雜因子（如吸菸史、職業暴露、腎臟疾病史或影像檢查頻率不同）影響。此外，雖然統計上顯示風險增加，但絕對發生率仍低，臨床意義需審慎解讀。對臨床實務而言，研究結果提醒醫師在具有腎臟癌高風險因子的患者中使用mirabegron 時應特別謹慎，但目前證據尚不足以改變膀胱過動症的標準治療策略。未來仍需前瞻性研究與機轉性研究，以釐清 β3-受體促效劑與腎臟癌之間是否存在真正的因果關係。

Objectives
To determine the effect of β3-adrenergic receptor (AR) agonist on the risk of kidney cancer in patients with overactive bladder (OAB).

Patients and methods
A nationwide population cohort study was conducted using data from the Korean National Health Insurance System database between January 2016 and December 2023. Validation analyses were performed using clinical data from patients with OAB treated with mirabegron or anticholinergics at a tertiary referral hospital between January 2014 and December 2023. The main exposure was intake of β3-AR agonist or anticholinergics, and the main outcome was incidence of kidney cancer.

Results
Of the 1 419 148 patients (61.6% male; median [interquartile range] age, 64 [53–73] years), 3229 developed kidney cancer after OAB treatment. The incidence rate of kidney cancer was 0.7 per 1000 person-years in the mirabegron group and 0.5 per 1000 person-years in the anticholinergic group. Among the validation data of 3108 patients (49.3% male; mean [standard deviation] age, 63.9 [13.3] years), 45 (1.4%) developed kidney cancer after OAB treatment. The mirabegron group had a higher incidence of kidney cancer (1.8%) than the anticholinergic group (0.7%) (P = 0.025).

Conclusions
Use of β3-AR agonists was associated with an increased risk of kidney cancer compared with anticholinergics. While these findings suggest a potential association between mirabegron use and kidney cancer, further studies are needed to confirm causality. Clinicians should exercise caution when prescribing mirabegron in patients with risk factors for kidney cancer.