Department of Diabetes, Endocrinology and Metabolism, Division of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Takeda Internal Medicine Clinic, Azumino 399-8304, Japan.
J Clin Endocrinol Metab. 2023 Aug 18;108(9):2203-2210. doi: 10.1210/clinem/dgad144.
Although adding spironolactone to renin-angiotensin system blockers reduces albuminuria in adults with chronic kidney disease and type 2 diabetes, it increases the risk of hyperkalemia.
To assess whether a lower dose of spironolactone (12.5 mg/d) reduces the risk of hyperkalemia while maintaining its effect on reducing albuminemia.
Multicenter, open-label, randomized controlled trial.
This study was conducted from July 2016 to November 2020 in ambulatory care at 3 diabetes medical institutions in Japan.
We enrolled 130 Japanese adults with type 2 diabetes and albuminuria (≥30 mg/gCre), estimated glomerular filtration rate ≥30 mL/min/1.73 m2, and serum potassium level <5.0 mEq/L.
The participants were randomly assigned to the spironolactone-administered and control groups.
Changes in urine albumin-to-creatinine ratio (UACR) from baseline over the 24-week interventional period.
The spironolactone group showed a significant reduction in UACR from baseline (mean decrease, 103.47 ± 340.80 mg/gCre) compared with the control group, which showed an increased UACR (mean increase, 63.93 ± 310.14 mg/gCre; P = .0007, Wilcoxon rank-sum test and t test). Although the spironolactone group had a statistically significant increase in serum potassium levels, none of the participants had a potassium level ≥5.5 mEq/L at 24 weeks. Further, participants with a higher initial serum potassium level tended to have a smaller increase (estimate, -0.37, analysis of covariance).
Low-dose spironolactone administration reduced albuminuria without causing hyperkalemia. Spironolactone administration, the oldest known and most cost-effective mineralocorticoid receptor antagonist, at lower doses should be reconsidered.
在患有慢性肾脏病和 2 型糖尿病的成年人中，加用血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂（angiotensin converting enzyme inhibitor/angiotensin receptor blocker，ACEI/ARB）可降低蛋白尿，但会增加高钾血症的风险。螺内酯是一种古老且经济有效的盐皮质激素受体拮抗剂，本研究旨在评估小剂量螺内酯（12.5 mg/d）是否可以在降低蛋白尿的同时降低高钾血症的风险。
评估小剂量螺内酯（12.5 mg/d）是否可以在降低蛋白尿的同时降低高钾血症的风险。
这是一项多中心、开放标签、随机对照试验。
这项研究于 2016 年 7 月至 2020 年 11 月在日本 3 家糖尿病医疗机构的门诊进行。
共纳入 130 例患有 2 型糖尿病且合并蛋白尿（≥30 mg/gCre）、估算肾小球滤过率（estimated glomerular filtration rate，eGFR）≥30 mL/min/1.73 m2 且血清钾水平<5.0 mEq/L 的日本成年人。
参与者被随机分配至螺内酯组和对照组。
在 24 周的干预期间，尿白蛋白与肌酐比值（urine albumin-to-creatinine ratio，UACR）从基线的变化。
与对照组相比，螺内酯组 UACR 从基线显著降低（平均降低 103.47 ± 340.80 mg/gCre），而对照组 UACR 升高（平均升高 63.93 ± 310.14 mg/gCre；P =.0007，Wilcoxon 秩和检验和 t 检验）。尽管螺内酯组血清钾水平有统计学意义上的升高，但在 24 周时无 1 例患者的血钾水平≥5.5 mEq/L。此外，初始血清钾水平较高的患者 UACR 降低幅度较小（协方差分析估计值为-0.37）。
小剂量螺内酯可降低蛋白尿，且不引起高钾血症。小剂量螺内酯（12.5 mg/d）治疗应该重新考虑，因为它是最早被发现的、且最经济有效的盐皮质激素受体拮抗剂。
