n patients with CKD and albuminuria, with and without type 2 diabetes. Methods: In this post-hoc analysis of the DAPA-CKD trial, 4304 adult patients with CKD were randomized to dapagliflozin 10mg or placebo as adjunct to maximally tolerated renin-angiotensin-system (RAAS) inhibitors. The primary endpoint was a composite of sustained ≥50% decline in estimated glomerular filtration rate, kidney failure, or death from kidney or cardiovascular cause. The kidney composite endpoint was similar but excluded cardiovascular death. We assessed associations among baseline albuminuria, early change in albuminuria, (baseline to Month 4), and residual albuminuria (Month 4) with the primary composite and kidney composite endpoints using Cox proportional hazards regression analyses. Results: Compared to placebo, dapagliflozin reduced urinary albumin-to-creatinine ratio (UACR; baseline to Month 4) by 36% (95% CI: 30.2%, 42.5%) and 21% (95% CI: 12, 30%) in participants with and without type 2 diabetes, respectively (p-interaction: 0.02). A reduction in UACR from baseline to Month 4 was associated with a lower risk for the primary and kidney composite endpoints with a similar risk gradient for participants with and without type 2 diabetes (p-interaction: 0.10 and 0.19, respectively). Residual albuminuria was associated with a similar risk for the primary and kidney composite endpoints in each treatment arm (p-interaction: 0.19 and 0.18, respectively). Conclusions: Dapagliflozin reduced albuminuria, and the magnitude of albuminuria reduction showed similar proportional reductions in risks for the primary and kidney composite endpoints in participants with and without type 2 diabetes. Patients with residual albuminuria at Month 4 – whether randomized to dapagliflozin or placebo – experienced relatively high rates of CKD progression kidney endpoints, suggesting that therapies added to RAAS inhibitors and dapagliflozin may be required to sustain kidney and cardiovascular health. Clinical trial registry name and registration number: A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease (DAPA-CKD), NCT03036150. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology...

中文翻译：

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基线、早期变化和残留白蛋白尿：达格列净治疗慢性肾脏病临床试验的事后分析


n 患有 CKD 和白蛋白尿的患者，伴有和没有 2 型糖尿病。方法： 在 DAPA-CKD 试验的事后分析中，4304 名成年 CKD 患者被随机分配至达格列净 10mg 或安慰剂组，作为最大耐受肾素-血管紧张素系统 （RAAS） 抑制剂的辅助治疗。主要终点是估计肾小球滤过率持续下降 ≥50%、肾衰竭或肾或心血管原因死亡的复合终点。肾脏复合终点相似，但排除了心血管死亡。我们使用 Cox 比例风险回归分析评估了基线白蛋白尿、白蛋白尿早期变化（基线至第 4 个月）和残余白蛋白尿（第 4 个月）与主要复合终点和肾脏复合终点之间的关联。结果：与安慰剂相比，达格列净使患有和非 2 型糖尿病的参与者的尿白蛋白/肌酐比值 （UACR;基线至第 4 个月） 分别降低了 36% （95% CI： 30.2%， 42.5%） 和 21% （95% CI： 12， 30%） （p 相互作用： 0.02）。从基线到第 4 个月的 UACR 降低与主要和肾脏复合终点的风险降低相关，患有和没有 2 型糖尿病的参与者的风险梯度相似 （p 交互作用： 分别为 0.10 和 0.19）。残余白蛋白尿与每个治疗组的主要终点和肾脏复合终点的风险相似相关 （p 交互作用： 分别为 0.19 和 0.18）。结论： 达格列净降低白蛋白尿，白蛋白尿减少的幅度显示 2 型糖尿病和非 2 型糖尿病参与者主要和肾脏复合终点的风险按相似比例降低。 第 4 个月时残留白蛋白尿的患者——无论是随机分配到达格列净还是安慰剂组——的 CKD 进展肾脏终点发生率相对较高，这表明可能需要在 RAAS 抑制剂和达格列净的基础上加入治疗来维持肾脏和心血管健康。临床试验注册名称和注册号：一项评估达格列净对慢性肾脏病患者肾脏结局和心血管死亡率影响的研究 （DAPA-CKD），NCT03036150。版权所有 © 2024 作者。由 Wolters Kluwer Health， Inc. 代表美国肾脏病学会出版...