Oka Kentaro, Masuda Takahiro, Ohara Ken, Miura Marina, Morinari Masato, Misawa Kyohei, Miyazawa Yasuharu, Akimoto Tetsu, Shimada Kazuyuki, Nagata Daisuke
Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Department of Nephrology, Shin-Oyama City Hospital, Oyama, Tochigi, Japan.
Front Med (Lausanne). 2023 Dec 14;10:1287066. doi: 10.3389/fmed.2023.1287066. eCollection 2023.
Sodium glucose cotransporter 2 (SGLT2) inhibitors have both glucose-lowering and diuretic effects. We recently reported that the SGLT2 inhibitor dapagliflozin exerts short-term fluid homeostatic action in patients with chronic kidney disease (CKD). However, the long-term effects of SGLT2 inhibitors on body fluid status in patients with CKD remain unclear. This was a prospective, non-randomized, open-label study that included a dapagliflozin treatment group ( = 73) and a control group ( = 24) who were followed for 6 months. Body fluid volume was measured using a bioimpedance analysis device. The extracellular water-to-total body water ratio (ECW/TBW), a predictor of renal outcomes, was used as a parameter for body fluid status (fluid retention, 0.400 ≤ ECW/TBW). Six-month treatment with dapagliflozin significantly decreased ECW/TBW compared with the control group (-0.65% ± 2.03% vs. 0.97% ± 2.49%, = 0.0018). Furthermore, dapagliflozin decreased the ECW/TBW in patients with baseline fluid retention, but not in patients without baseline fluid retention (-1.47% ± 1.93% vs. -0.01% ± 1.88%, = 0.0017). Vasopressin surrogate marker copeptin levels were similar between the control and dapagliflozin groups at 6 months (32.3 ± 33.4 vs. 30.6 ± 30.1 pmol/L, = 0.8227). However, dapagliflozin significantly increased the change in copeptin levels at 1 week (39.0% ± 41.6%, = 0.0010), suggesting a compensatory increase in vasopressin secretion to prevent hypovolemia. Renin and aldosterone levels were similar between the control and dapagliflozin groups at 6 months, while epinephrine and norepinephrine (markers of sympathetic nervous system activity) were significantly lower in the dapagliflozin group than in the control group. In conclusion, the SGLT2 inhibitor dapagliflozin ameliorated fluid retention and maintained euvolemic fluid status in patients with CKD, suggesting that SGLT2 inhibitors exert sustained fluid homeostatic actions in patients with various fluid backgrounds. Clinical trial registration: https://www.umin.ac.jp/ctr/, identifier [UMIN000048568].
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂具有降糖和利尿作用。我们最近报道，SGLT2抑制剂达格列净对慢性肾脏病（CKD）患者具有短期的液体稳态作用。然而，SGLT2抑制剂对CKD患者体液状态的长期影响仍不清楚。这是一项前瞻性、非随机、开放标签研究，包括一个达格列净治疗组（n = 73）和一个对照组（n = 24），随访6个月。使用生物电阻抗分析仪测量体液量。细胞外水与总体水的比值（ECW/TBW）是肾脏预后的一个预测指标，被用作体液状态（液体潴留，0.400≤ECW/TBW）的参数。与对照组相比，达格列净治疗6个月显著降低了ECW/TBW（-0.65%±2.03%对0.97%±2.49%，P = 0.0018）。此外，达格列净降低了基线时有液体潴留患者的ECW/TBW，但对基线时无液体潴留的患者没有影响（-1.47%±1.93%对-0.01%±1.88%，P = 0.0017）。6个月时，对照组和达格列净组的血管加压素替代标志物 copeptin 水平相似（32.3±33.4对30.6±30.1 pmol/L，P = 0.8227）。然而，达格列净在1周时显著增加了copeptin水平的变化（39.0%±41.6%，P = 0.0010），提示血管加压素分泌代偿性增加以预防血容量不足。6个月时，对照组和达格列净组的肾素和醛固酮水平相似，而达格列净组的肾上腺素和去甲肾上腺素（交感神经系统活动标志物）显著低于对照组。总之，SGLT2抑制剂达格列净改善了CKD患者的液体潴留并维持了正常血容量的体液状态，提示SGLT2抑制剂在不同体液背景的患者中发挥持续的液体稳态作用。临床试验注册：https://www.umin.ac.jp/ctr/，标识符[UMIN000048568] 。
