Department of Renal Medicine, University College London, London, UK.
Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Nephrol Dial Transplant. 2020 Oct 1;35(10):1700-1711. doi: 10.1093/ndt/gfaa234.
The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials.
In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol).
Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1 mL/min/1.73 m2 lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR).
Participants with a wide range of underlying kidney diseases receiving renin-angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2-4 and increased albuminuria, with and without T2D.
达格列净和慢性肾脏病不良结局预防（DAPA-CKD；NCT03036150）试验旨在评估钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂达格列净对伴有和不伴有 2 型糖尿病（T2D）的慢性肾脏病（CKD）患者的肾脏和心血管结局的影响。本分析报告了招募参与者的基线特征，并将其与其他试验中招募的参与者进行了比较。
在 DAPA-CKD 中，4304 名尿白蛋白与肌酐比值（UACR）≥200mg/g 和估计肾小球滤过率（eGFR）在 25 至 75ml/min/1.73m2 之间的参与者被随机分配至达格列净 10mg 每日一次或安慰剂。平均 eGFR 为 43.1ml/min/1.73m2，中位数 UACR 为 949mg/g（108mg/mmol）。
总体而言，2906 名参与者（68%）患有 T2D，其中 396 名患有归因于糖尿病以外原因的 CKD。糖尿病后 CKD 的最常见原因（n=2510）为缺血性/高血压性肾病（n=687）和慢性肾小球肾炎（n=695），其中免疫球蛋白 A 肾病（n=270）最为常见。共有 4174 名参与者（97%）正在接受血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂治疗，1882 名（43.7%）正在接受利尿剂治疗，229 名（5.3%）正在接受盐皮质激素受体拮抗剂治疗，122 名（2.8%）正在接受胰高血糖素样肽 1 受体激动剂治疗。与卡格列净和在有既定肾病的糖尿病患者中的肾脏事件的临床评估（CREDENCE）不同，DAPA-CKD 试验招募了因糖尿病和非糖尿病原因导致 CKD 的参与者。DAPA-CKD 试验参与者的平均 eGFR 比 CREDENCE 低 13.1ml/min/1.73m2，与 FIDELIO-DKD 试验和研究糖尿病肾病与 AtRasentan（SONAR）试验中的相似。
该试验招募了患有多种基础肾脏疾病且正在接受肾素-血管紧张素系统阻断治疗的参与者。该试验将评估达格列净在伴有和不伴有 2 型糖尿病的 CKD 2-4 期和白蛋白尿增加的参与者中的疗效和安全性。
