Effect of dapagliflozin on urinary albumin excretion in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial

医学 蛋白尿 达帕格列嗪 肾脏疾病 肾功能 微量白蛋白尿 泌尿科 内科学 2型糖尿病 糖尿病 安慰剂 肌酐 内分泌学 病理 替代医学
作者
Niels Jongs,Tom Greene,Glenn M. Chertow,John J.V. McMurray,Anna Maria Langkilde,Ricardo Correa‐Rotter,Peter Rossing,C. David Sjöström,Bergur V. Stefánsson,Robert D. Toto,David C. Wheeler,Hiddo J.L. Heerspink
出处
期刊:The Lancet Diabetes & Endocrinology [Elsevier]
卷期号:9 (11): 755-766 被引量:124
标识
DOI:10.1016/s2213-8587(21)00243-6
摘要

Background Reductions in albuminuria are associated with a subsequent lower risk of kidney failure in patients with chronic kidney disease. The SGLT2 inhibitor dapagliflozin significantly reduced albuminuria in patients with type 2 diabetes and normal or near-normal kidney function. Whether this effect persists in patients with chronic kidney disease with and without type 2 diabetes is unknown. We assessed the effects of dapagliflozin on albuminuria in patients with chronic kidney disease with and without type 2 diabetes in the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial. Methods DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 sites in 21 countries. Patients were eligible for the trial if they had chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) between 25 mL/min per 1·73 m2 and 75 mL/min per 1·73 m2 and a urinary albumin-to-creatinine ratio (UACR) between 200 mg/g and 5000 mg/g (22·6 to 565·6 mg/mmol). Participants were randomly assigned to dapagliflozin 10 mg (AstraZeneca; Gothenburg, Sweden) once daily or matching placebo, in accordance with the sequestered, fixed randomisation schedule, using balanced blocks to ensure an approximate 1:1 ratio. Change in albuminuria was a pre-specified exploratory outcome of DAPA-CKD. Regression in UACR stage, defined as a transition from macroalbuminuria (≥300 mg/g) to microalbuminuria or normoalbuminuria (<300 mg/g), and progression in UACR stage, defined as a transition from less than 3000 mg/g to 3000 mg/g or greater, were additional discrete endpoints. The trial is registered with ClinicalTrials.gov, NCT03036150. Findings Between Feb 2, 2017, and April 3, 2020, 4304 patients were recruited and randomly assigned to either dapagliflozin (n=2152) or placebo (n=2152). Median UACR was 949 mg/g (IQR 477 to 1885). Overall, compared with placebo, dapagliflozin reduced geometric mean UACR by 29·3% (95% CI –33·1 to –25·2; p<0·0001); relative to placebo, treatment with dapagliflozin resulted in a geometric mean percentage change of −35·1% (95% CI −39·4 to −30·6; p<0·0001) in patients with type 2 diabetes and −14·8% (−22·9 to −5·9; p=0·0016) in patients without type 2 diabetes over the follow-up visits (pinteraction<0·0001) Among 3860 patients with UACR of 300 mg/g or greater at baseline, dapagliflozin increased the likelihood of regression in UACR stage (hazard ratio 1·81, 95% CI 1·60 to 2·05). Among 3820 patients with UACR less than 3000 mg/g at baseline, dapagliflozin decreased the risk of progression in UACR stage (0·41, 0·32 to 0·52). Larger reductions in UACR at day 14 during dapagliflozin treatment were significantly associated with attenuated eGFR decline during subsequent follow-up (β per log unit UACR change –3·06, 95% CI –5·20 to –0·90; p=0·0056). Interpretation In patients with chronic kidney disease with and without type 2 diabetes, dapagliflozin significantly reduced albuminuria, with a larger relative reduction in patients with type 2 diabetes. The similar effects of dapagliflozin on clinical outcomes in patients with or without type 2 diabetes, but different effects on UACR, suggest that part of the protective effect of dapagliflozin in patients with chronic kidney disease might be mediated through pathways unrelated to reduction in albuminuria. Funding AstraZeneca.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
VickyZWY发布了新的文献求助10
2秒前
瘦瘦的冬天完成签到,获得积分10
5秒前
ss13l完成签到,获得积分10
7秒前
潘潘完成签到,获得积分10
7秒前
大模型应助Adel采纳,获得10
8秒前
2123121321321完成签到,获得积分10
8秒前
乐乐应助科研小白采纳,获得10
9秒前
我感觉先有蛋完成签到,获得积分10
14秒前
huahua发布了新的文献求助10
14秒前
甜甜圈发布了新的文献求助10
16秒前
CDabin完成签到,获得积分10
19秒前
21秒前
Adel发布了新的文献求助10
21秒前
刘晓倩发布了新的文献求助10
24秒前
++完成签到 ,获得积分10
33秒前
buhuidanhuixue完成签到,获得积分10
37秒前
小月完成签到,获得积分10
38秒前
甜甜圈完成签到,获得积分10
38秒前
珍珠奶茶完成签到,获得积分10
40秒前
42秒前
44秒前
SciGPT应助桔梗采纳,获得10
50秒前
Hello应助hgh采纳,获得10
52秒前
55秒前
VickyZWY完成签到 ,获得积分20
57秒前
可靠橘子发布了新的文献求助10
59秒前
动听靖完成签到 ,获得积分10
59秒前
1分钟前
1分钟前
半糖神仙完成签到 ,获得积分20
1分钟前
自渡完成签到 ,获得积分10
1分钟前
1分钟前
hgh发布了新的文献求助10
1分钟前
ss12完成签到,获得积分10
1分钟前
Lee完成签到 ,获得积分10
1分钟前
ZDZ发布了新的文献求助10
1分钟前
1分钟前
1分钟前
eris完成签到 ,获得积分10
1分钟前
1分钟前
高分求助中
Sustainability in Tides Chemistry 2800
Kinetics of the Esterification Between 2-[(4-hydroxybutoxy)carbonyl] Benzoic Acid with 1,4-Butanediol: Tetrabutyl Orthotitanate as Catalyst 1000
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
Rechtsphilosophie 1000
Bayesian Models of Cognition:Reverse Engineering the Mind 888
Handbook of Qualitative Cross-Cultural Research Methods 600
Very-high-order BVD Schemes Using β-variable THINC Method 568
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3137664
求助须知:如何正确求助?哪些是违规求助? 2788576
关于积分的说明 7787679
捐赠科研通 2444950
什么是DOI,文献DOI怎么找? 1300139
科研通“疑难数据库(出版商)”最低求助积分说明 625814
版权声明 601023