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A randomized, open-label, clinical trial examined the effects of canagliflozin on albuminuria and eGFR decline using an individual pre-intervention eGFR slope
Kidney International ( IF 14.8 ) Pub Date : 2024-08-30 , DOI: 10.1016/j.kint.2024.08.019
Satoshi Miyamoto 1 , Hiddo J L Heerspink 2 , Dick de Zeeuw 2 , Kota Sakamoto 3 , Michihiro Yoshida 3 , Masao Toyoda 4 , Daisuke Suzuki 5 , Takashi Hatanaka 6 , Tohru Nakamura 7 , Shinji Kamei 8 , Satoshi Murao 9 , Kazuyuki Hida 10 , Shinichiro Ando 11 , Hiroaki Akai 12 , Yasushi Takahashi 13 , Munehiro Kitada 14 , Hisashi Sugano 15 , Tomokazu Nunoue 16 , Akihiko Nakamura 17 , Motofumi Sasaki 18 , Tatsuaki Nakatou 19 , Kei Fujimoto 20 , Daiji Kawanami 21 , Takashi Wada 22 , Nobuyuki Miyatake 23 , Hiromi Kuramoto 3 , Kenichi Shikata 3 ,
Kidney International ( IF 14.8 ) Pub Date : 2024-08-30 , DOI: 10.1016/j.kint.2024.08.019
Satoshi Miyamoto 1 , Hiddo J L Heerspink 2 , Dick de Zeeuw 2 , Kota Sakamoto 3 , Michihiro Yoshida 3 , Masao Toyoda 4 , Daisuke Suzuki 5 , Takashi Hatanaka 6 , Tohru Nakamura 7 , Shinji Kamei 8 , Satoshi Murao 9 , Kazuyuki Hida 10 , Shinichiro Ando 11 , Hiroaki Akai 12 , Yasushi Takahashi 13 , Munehiro Kitada 14 , Hisashi Sugano 15 , Tomokazu Nunoue 16 , Akihiko Nakamura 17 , Motofumi Sasaki 18 , Tatsuaki Nakatou 19 , Kei Fujimoto 20 , Daiji Kawanami 21 , Takashi Wada 22 , Nobuyuki Miyatake 23 , Hiromi Kuramoto 3 , Kenichi Shikata 3 ,
Affiliation
Demonstrating drug efficacy in slowing kidney disease progression requires large clinical trials when targeting participants with an early stage of chronic kidney disease (CKD). In this randomized, parallel-group, open-labeled trial (CANPIONE study), we assessed the effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin using the individual’s change in estimated glomerular filtration rate (eGFR) slope before (pre-intervention slope) and during treatment (chronic slope). We randomly assigned (1:1) participants with type 2 diabetes, urinary albumin-to-creatinine ratio (UACR) of 50 to under 300 mg/g, and an eGFR of at least 45 ml/min/1.73m2 to receive canagliflozin or guideline-recommended treatment except for SGLT2 inhibitors (control). The first and second primary outcomes were the geometric mean percentage change from baseline in UACR and the change in eGFR slope, respectively. Of 98 randomized participants, 96 received at least one study treatment. The least-squares mean change from baseline in log-transformed geometric mean UACR was significantly greater in the canagliflozin group than the control group (between group-difference, −30.8% (95% confidence interval −42.6 to −16.8). The between-group difference (canagliflozin group – control group) of change in eGFR slope (chronic – pre-intervention) was 4.4 (1.6 to 7.3) ml/min/1.73 m2 per year, which was more pronounced in participants with faster eGFR decline. In summary, canagliflozin reduced albuminuria and the participant-specific natural course of eGFR decline in participants with type 2 diabetes and microalbuminuria. Thus, the CANPIONE study suggests that the within-individual change in eGFR slope may be a novel approach to determine the kidney protective potential of new therapies in early stages of CKD.
中文翻译:
一项随机、开放标签、临床试验使用个体干预前 eGFR 斜率检查了卡格列净对白蛋白尿和 eGFR 下降的影响
要证明药物在减缓肾脏疾病进展方面的疗效,需要针对慢性肾脏病 (CKD) 早期参与者进行大型临床试验。在这项随机、平行组、开放标签试验 (CANPIONE 研究) 中,我们使用个体在治疗前 (干预前斜率) 和治疗期间 (慢性斜率) 的估计肾小球滤过率 (eGFR) 斜率的变化来评估钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂卡格列净的效果。我们将 (1:1) 患有 2 型糖尿病、尿白蛋白与肌酐比值 (UACR) 为 50 至 300 mg/g 以下且 eGFR 至少为 45 ml/min/1.73m2 的参与者随机分配接受卡格列净或指南推荐的治疗,但 SGLT2 抑制剂除外(对照)。第一和第二主要结局分别是 UACR 相对于基线的几何平均百分比变化和 eGFR 斜率的变化。在 98 名随机参与者中,96 名至少接受了一种研究治疗。卡格列净组对数转换几何平均 UACR 相对于基线的最小二乘平均变化显著大于对照组 (组间差异,-30.8% (95% 置信区间 -42.6 至 -16.8)。eGFR 斜率(慢性 - 干预前)变化的组间差异(卡格列净组 - 对照组)为每年 4.4 (1.6 至 7.3) ml/min/1.73 m2,这在 eGFR 下降较快的参与者中更为明显。总之,卡格列净减少了 2 型糖尿病和微量白蛋白尿参与者的白蛋白尿和 eGFR 下降的参与者特异性自然过程。 因此,CANPIONE 研究表明,eGFR 斜率的个体内变化可能是确定 CKD 早期新疗法对肾脏保护潜力的新方法。
更新日期:2024-08-30
中文翻译:
一项随机、开放标签、临床试验使用个体干预前 eGFR 斜率检查了卡格列净对白蛋白尿和 eGFR 下降的影响
要证明药物在减缓肾脏疾病进展方面的疗效,需要针对慢性肾脏病 (CKD) 早期参与者进行大型临床试验。在这项随机、平行组、开放标签试验 (CANPIONE 研究) 中,我们使用个体在治疗前 (干预前斜率) 和治疗期间 (慢性斜率) 的估计肾小球滤过率 (eGFR) 斜率的变化来评估钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂卡格列净的效果。我们将 (1:1) 患有 2 型糖尿病、尿白蛋白与肌酐比值 (UACR) 为 50 至 300 mg/g 以下且 eGFR 至少为 45 ml/min/1.73m2 的参与者随机分配接受卡格列净或指南推荐的治疗,但 SGLT2 抑制剂除外(对照)。第一和第二主要结局分别是 UACR 相对于基线的几何平均百分比变化和 eGFR 斜率的变化。在 98 名随机参与者中,96 名至少接受了一种研究治疗。卡格列净组对数转换几何平均 UACR 相对于基线的最小二乘平均变化显著大于对照组 (组间差异,-30.8% (95% 置信区间 -42.6 至 -16.8)。eGFR 斜率(慢性 - 干预前)变化的组间差异(卡格列净组 - 对照组)为每年 4.4 (1.6 至 7.3) ml/min/1.73 m2,这在 eGFR 下降较快的参与者中更为明显。总之,卡格列净减少了 2 型糖尿病和微量白蛋白尿参与者的白蛋白尿和 eGFR 下降的参与者特异性自然过程。 因此,CANPIONE 研究表明,eGFR 斜率的个体内变化可能是确定 CKD 早期新疗法对肾脏保护潜力的新方法。