NEJM：达格列净治疗慢性肾脏病可显著改善预后

慢性肾脏病患者的肾脏和心血管不良结局的风险较高。达格列净治疗伴或不伴2型糖尿病的慢性肾脏病患者的疗效目前尚不清楚。

研究组招募了4304名参与者，其肾小球滤过率（GFR）为25-75ml/min/1.73m2（体表面积），尿白蛋白与肌酐的比率（白蛋白以毫克计，肌酐以克计）在200至5000之间，将其随机分组，其中2152名接受达格列净治疗，2152名接受安慰剂治疗。主要结局是估计GFR持续下降至少50%、终末期肾病、肾脏或心血管原因死亡的综合结局。

平均治疗2.4年后，达格列净组中有197名（9.2%）发生主要结局，安慰剂组中有312名（15.4%），风险比为0.61，差异显著。估计GFR持续下降至少50%、终末期肾病或因肾脏原因死亡的综合风险比为0.56，心血管原因死亡或因心力衰竭住院的综合风险比为0.71。达格列净组中有101名参与者（4.7%）死亡，显著低于安慰剂组（146名，6.8%），风险比为0.69。达格列净治疗有2型糖尿病或没有2型糖尿病患者的疗效相差不大，证实了达格列净的安全性。

总之，对于慢性肾脏病患者，无论其是否有糖尿病，采用达格列净治疗，与安慰剂相比，可显著改善患者预后。

附：英文原文

Title:Dapagliflozin in Patients with Chronic Kidney Disease

Author: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., et al., for the DAPA-CKD Trial Committees and Investigators*

Issue&Volume:September 24, 2020

Abstract:

BACKGROUND

Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known.

METHODS

We randomly assigned 4304 participants with an estimated glomerular filtration rate (GFR) of 25 to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 200 to 5000 to receive dapagliflozin (10 mg once daily) or placebo. The primary outcome was a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes.

RESULTS

The independent data monitoring committee recommended stopping the trial because of efficacy. Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001; number needed to treat to prevent one primary outcome event, 19 [95% CI, 15 to 27]). The hazard ratio for the composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was 0.56 (95% CI, 0.45 to 0.68; P<0.001), and the hazard ratio for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI, 0.55 to 0.92; P=0.009). Death occurred in 101 participants (4.7%) in the dapagliflozin group and 146 participants (6.8%) in the placebo group (hazard ratio, 0.69; 95% CI, 0.53 to 0.88; P=0.004). The effects of dapagliflozin were similar in participants with type 2 diabetes and in those without type 2 diabetes. The known safety profile of dapagliflozin was confirmed.

CONCLUSIONS

Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo. (Funded by AstraZeneca; DAPA-CKD ClinicalTrials.gov number, NCT03036150. opens in new tab.)

DOI:DOI: 10.1056/NEJMoa2024816

Source:https://www.nejm.org/doi/full/10.1056/NEJMoa2024816