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达格列净治疗慢性肾脏病患者
Dapagliflozin in Patients with Chronic Kidney Disease


Hiddo J.L. Heerspink ... 其他 • 2020.10.08
相关阅读
• KDIGO发布2020年慢性肾脏病患者糖尿病管理指南 • 达格列净治疗后的肾脏结局 • 达格列净治疗射血分数降低的心力衰竭患者 • 达格列净对心脏收缩功能降低的心力衰竭患者的各阶段糖尿病的治疗作用 • 卡格列净与2型糖尿病合并肾病患者的肾脏结局之间的关系

摘要


背景

慢性肾脏病患者发生肾脏和心血管不良结局的风险高。达格列净对合并或未合并2型糖尿病的慢性肾脏病患者的疗效尚未明确。

 

方法

我们将估计肾小球滤过率(GFR)为25~75 ml/(min·1.73 m2),并且尿白蛋白/肌酐(白蛋白的单位为mg,肌酐的单位为g)为200~5,000的4,304例参与者随机分组,两组分别接受达格列净(每日1次,每次10 mg)或安慰剂治疗。主要结局是由估计GFR持续降低≥50%、终末期肾脏病或者肾脏或心血管原因死亡构成的复合结局。

 

结果

独立的数据监察委员会因达格列净疗效明确而建议终止试验。在中位2.4年期间,达格列净组2,152例参与者中的197例(9.2%)和安慰剂组2,152参与者中的312例(14.5%)发生了主要结局事件(风险比,0.61;95%置信区间[CI],0.51~0.72;P<0.001;每预防1起主要结局事件所需治疗例数,19[95% CI,15~27])。由估计GFR持续降低≥50%、终末期肾脏病或肾脏原因死亡构成的复合终点的风险比为0.56(95% CI,0.45~0.68;P<0.001),由心血管原因死亡或因心力衰竭住院构成的复合终点的风险比为0.71(95% CI,0.55~0.92;P=0.009)。达格列净组101例参与者(4.7%)和安慰剂组146例参与者(6.8%)死亡(风险比,0.69;95% CI,0.53~0.88;P=0.004)。达格列净在患2型糖尿病和未患2型糖尿病的参与者产生的疗效相似。达格列净的已知安全性得到证实。

 

结论

在慢性肾脏病患者中,不论其是否合并糖尿病,达格列净组的复合结局(由估计GFR持续降低≥50%、终末期肾脏病或者肾脏或心血管原因死亡构成)风险均显著低于安慰剂组(由阿斯利康资助,DAPA-CKD在ClinicalTrials.gov注册号为NCT03036150)。





作者信息

Hiddo J.L. Heerspink, Ph.D., Bergur V. Stefánsson, M.D., Ricardo Correa-Rotter, M.D., Glenn M. Chertow, M.D., Tom Greene, Ph.D., Fan-Fan Hou, M.D., Johannes F.E. Mann, M.D., John J.V. McMurray, M.D., Magnus Lindberg, M.Sc., Peter Rossing, M.D., C. David Sjöström, M.D., Roberto D. Toto, M.D., Anna-Maria Langkilde, M.D., and David C. Wheeler, M.D. for the DAPA-CKD Trial Committees and Investigators*
From the Department Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands (H.J.L.H.); the George Institute for Global Health, Sydney (H.J.L.H., D.C.W.); Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden (B.V.S., M.L., C.D.S., A.-M.L.); the National Medical Science and Nutrition Institute Salvador Zubirán, Mexico City (R.C.-R.); the Departments of Medicine and Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA (G.M.C.); the Study Design and Biostatistics Center, University of Utah Health Sciences, Salt Lake City (T.G.); the Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, Guangzhou, China (F.-F.H.); KfH Kidney Center, Munich, and Department of Medicine 4, University of Erlangen–Nuremberg, Erlangen — both in Germany (J.F.E.M.); the Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow (J.J.V.M.), and the Department of Renal Medicine, University College London, London (D.C.W.) — both in the United Kingdom; Steno Diabetes Center Copenhagen, Gentofte, and the Department of Clinical Medicine, University of Copenhagen, Copenhagen — both in Denmark (P.R.); and the Department of Internal Medicine, UT Southwestern Medical Center, Dallas (R.D.T.). Address reprint requests to Dr. Heerspink at the Department of Clinical Pharmacy and Pharmacology, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, the Netherlands, or at h.j.lambers.heerspink@umcg.nl. *A complete list of DAPA-CKD committee members and investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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