Division of Nephrology and Endocrinology, The University of Tokyo School of Medicine, Tokyo, 113-8655, Japan.
Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Clin Exp Nephrol. 2024 Jun;28(6):588-595. doi: 10.1007/s10157-024-02489-4. Epub 2024 Apr 20.
EMPA-KIDNEY assessed the effects of empagliflozin 10 mg once daily vs. placebo in 6609 patients with chronic kidney disease (CKD) at risk of progression, including 612 participants from Japan.
Eligibility required an estimated glomerular filtration rate (eGFR) of ≥ 20 < 45; or ≥ 45 < 90 ml/min/1.73m with a urinary albumin-to-creatinine ratio (uACR) of ≥ 200 mg/g. The primary outcome was a composite of kidney disease progression (end-stage kidney disease, a sustained eGFR decline to < 10 ml/min/1.73m or ≥ 40% from randomization, or renal death) or cardiovascular death. In post-hoc analyses, we explored the effects of empagliflozin in participants from Japan vs. non-Japan regions, including additional models assessing whether differences in treatment effects between these regions could result from differences in baseline characteristics.
Japanese participants had higher levels of albuminuria and eGFR than those from non-Japan regions. During a median of 2.0 year follow-up, a primary outcome occurred in 432 patients (13.1%) in the empagliflozin group and in 558 patients (16.9%) in the placebo group (hazard ratio [HR], 0.72, 95% confidence interval [95%CI] 0.64-0.82; P < 0.0001). Among the participants from non-Japan regions, there were 399 vs. 494 primary outcomes (0.75, 0.66-0.86), and 33 vs. 64 (0.49, 0.32-0.75; heterogeneity p = 0.06) in Japan. Results were similar when models explicitly considered treatment interactions with diabetes status, categories of eGFR/uACR, and recruitment in Japan (heterogeneity p = 0.08). Safety outcomes were broadly comparable between the two groups, and by Japanese status.
Empagliflozin safely reduced the risk of "kidney disease progression or cardiovascular death" in patients with CKD, with consistent effects in participants from Japan.
EMPA-KIDNEY 评估了每日一次 empagliflozin 10 毫克与安慰剂在 6609 名有进展风险的慢性肾脏病（CKD）患者中的疗效，其中包括 612 名来自日本的参与者。
入选标准要求估算肾小球滤过率（eGFR）≥20<45；或≥45<90 ml/min/1.73m，尿白蛋白与肌酐比值（uACR）≥200 mg/g。主要终点是肾脏疾病进展（终末期肾病，eGFR 持续下降至<10 ml/min/1.73m或自随机分组起下降≥40%，或肾脏死亡）或心血管死亡的复合终点。在事后分析中，我们探讨了 empagliflozin 在日本与非日本地区参与者中的疗效，包括评估这些地区治疗效果差异是否可能源于基线特征差异的附加模型。
日本参与者的白蛋白尿和 eGFR 水平高于非日本地区参与者。在中位 2.0 年的随访期间，在 empagliflozin 组中有 432 例（13.1%）患者发生主要终点事件，而在安慰剂组中有 558 例（16.9%）患者发生主要终点事件（风险比 [HR]，0.72，95%置信区间 [95%CI] 0.64-0.82；P<0.0001）。在非日本地区参与者中，主要终点事件分别为 399 例和 494 例（0.75，0.66-0.86），日本地区分别为 33 例和 64 例（0.49，0.32-0.75；异质性 p=0.06）。当模型明确考虑到糖尿病状态、eGFR/uACR 类别和日本招募的治疗作用相互作用时，结果相似（异质性 p=0.08）。两组间安全性结局大致相似，且按日本状态划分时亦相似。
empagliflozin 可安全降低 CKD 患者的“肾脏疾病进展或心血管死亡”风险，在日本参与者中疗效一致。
