Department of Renal Medicine, University College London, London, UK.
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Nephrol Dial Transplant. 2022 Aug 22;37(9):1647-1656. doi: 10.1093/ndt/gfab335.
BACKGROUND: Despite renin-angiotensin-aldosterone system blockade and immunosuppressive treatment, focal segmental glomerulosclerosis (FSGS) often progresses to kidney failure. The objective of this prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease trial (DAPA-CKD) was to assess efficacy and safety of dapagliflozin in a small subgroup of participants with FSGS confirmed by kidney biopsy. METHODS: In DAPA-CKD, patients with an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2 and urinary albumin:creatinine ratio (UACR) 200-5000 mg/g (22.6-565 mg/mol) were randomized to dapagliflozin 10 mg once daily or placebo as an adjunct to standard care and followed for median 2.4 years. The primary composite endpoint was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The endpoint of interest for this analysis was eGFR slope (acute effects from baseline to Week 2 and chronic effects from Week 2 to end of treatment). RESULTS: Of 104 participants with biopsy-confirmed FSGS, 45 were randomized to dapagliflozin and 59 to placebo. Mean (standard deviation) age was 54.0 (14.3) years, mean eGFR 41.9 (11.5) mL/min/1.73 m2 and median (interquartile range) UACR 1248 (749-2211) mg/g. The primary outcome occurred in 4 (8.9%) and 7 (11.9%) participants randomized to dapagliflozin and placebo, respectively [hazard ratio 0.62, 95% confidence interval (95% CI) 0.17, 2.17]. Dapagliflozin led to a larger acute reduction (standard error) in eGFR compared with placebo (-4.5, 95% CI -5.9 to -3.1 versus -0.9, -2.1 to 0.4 mL/min/1.73 m2/2 weeks). Thereafter, mean rates of chronic eGFR decline with dapagliflozin and placebo were -1.9 (-3.0, -0.9) and -4.0 (-4.9, -3.0) mL/min/1.73 m2/year, respectively (difference 2.0, 95% CI 0.6 to 3.5, mL/min/1.73 m2/year). Adverse events leading to study drug discontinuation were similar in both groups; there were fewer serious adverse events with dapagliflozin. CONCLUSIONS: Among DAPA-CKD participants with FSGS, dapagliflozin reduced the rate of chronic decline of eGFR compared with placebo, although this difference was not statistically significant.
背景：尽管进行了肾素-血管紧张素-醛固酮系统阻断和免疫抑制治疗，局灶节段性肾小球硬化症（FSGS）仍常进展为肾衰竭。本研究旨在评估达格列净在经肾活检证实为 FSGS 的小亚组患者中的疗效和安全性，这是 DAPA-CKD 试验（达格列净预防慢性肾脏病不良结局）的一项预设分析。
方法：在 DAPA-CKD 中，肾小球滤过率（eGFR）估计值为 25-75mL/min/1.73 m2 且尿白蛋白/肌酐比值（UACR）为 200-5000mg/g（22.6-565mg/mol）的患者被随机分为达格列净 10mg 每日一次或安慰剂，作为标准治疗的辅助治疗，并随访中位数 2.4 年。主要复合终点为 eGFR 持续下降≥50%、终末期肾病、或肾脏或心血管死亡。本分析的终点是 eGFR 斜率（从基线到第 2 周的急性效应和从第 2 周到治疗结束的慢性效应）。
结果：在 104 名经活检证实为 FSGS 的患者中，45 名被随机分配至达格列净组，59 名被随机分配至安慰剂组。平均（标准差）年龄为 54.0（14.3）岁，平均 eGFR 为 41.9（11.5）mL/min/1.73 m2，中位数（四分位间距）UACR 为 1248（749-2211）mg/g。达格列净组和安慰剂组分别有 4（8.9%）和 7（11.9%）名患者发生主要结局[风险比 0.62，95%置信区间（95%CI）0.17，2.17]。与安慰剂相比，达格列净导致更大的急性 eGFR 下降（标准误差）（-4.5，95%CI -5.9 至 -3.1 与 -0.9，-2.1 至 0.4 mL/min/1.73 m2/2 周）。此后，达格列净和安慰剂组的慢性 eGFR 年下降平均值分别为-1.9（-3.0，-0.9）和-4.0（-4.9，-3.0）mL/min/1.73 m2/年（差值 2.0，95%CI 0.6 至 3.5，mL/min/1.73 m2/年）。两组导致研究药物停药的不良事件相似；达格列净组的严重不良事件较少。
结论：在 DAPA-CKD 中 FSGS 患者中，与安慰剂相比，达格列净降低了 eGFR 慢性下降的速度，但差异无统计学意义。
Nephrol Dial Transplant. 2020-10-1
J Am Soc Nephrol. 2021-9
J Clin Med. 2025-5-18
Biomolecules. 2025-2-14
Kidney Int Rep. 2024-9-24
Kidney Res Clin Pract. 2025-1
N Engl J Med. 2020-9-24
Nephrol Dial Transplant. 2020-10-1
Am J Kidney Dis. 2021-2
Zotero 插件
