Department of Renal Medicine, University College London, London, UK; The George Institute for Global Health, Sydney, Australia.
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
Kidney Int. 2021 Jul;100(1):215-224. doi: 10.1016/j.kint.2021.03.033. Epub 2021 Apr 18.
Immunoglobulin A (IgA) nephropathy is a common form of glomerulonephritis, which despite use of renin-angiotensin-aldosterone-system blockers and immunosuppressants, often progresses to kidney failure. In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial, dapagliflozin reduced the risk of kidney failure and prolonged survival in participants with chronic kidney disease with and without type 2 diabetes, including those with IgA nephropathy. Participants with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m and urinary albumin-to-creatinine ratio 200-5000 mg/g (22.6-565 mg/mol) were randomized to dapagliflozin 10mg or placebo, as adjunct to standard care. The primary composite endpoint was a sustained decline in eGFR of 50% or more, end-stage kidney disease, or death from a kidney disease-related or cardiovascular cause. Of 270 participants with IgA nephropathy (254 [94%] confirmed by previous biopsy), 137 were randomized to dapagliflozin and 133 to placebo, and followed for median 2.1 years. Overall, mean age was 51.2 years; mean eGFR, 43.8 mL/min/1.73m; and median urinary albumin-to-creatinine ratio, 900 mg/g. The primary outcome occurred in six (4%) participants on dapagliflozin and 20 (15%) on placebo (hazard ratio, 0.29; 95% confidence interval, 0.12, 0.73). Mean rates of eGFR decline with dapagliflozin and placebo were -3.5 and -4.7 mL/min/1.73m/year, respectively. Dapagliflozin reduced the urinary albumin-to-creatinine ratio by 26% relative to placebo. Adverse events leading to study drug discontinuation were similar with dapagliflozin and placebo. There were fewer serious adverse events with dapagliflozin, and no new safety findings in this population. Thus, in participants with IgA nephropathy, dapagliflozin reduced the risk of chronic kidney disease progression with a favorable safety profile.
免疫球蛋白 A（IgA）肾病是一种常见的肾小球肾炎，尽管使用了肾素-血管紧张素-醛固酮系统阻滞剂和免疫抑制剂，它仍常常进展为肾衰竭。在达格列净预防慢性肾脏病不良结局试验中，达格列净降低了伴有或不伴有 2 型糖尿病的慢性肾脏病患者的肾衰竭风险并延长了其生存时间，其中包括 IgA 肾病患者。估算肾小球滤过率（eGFR）为 25-75 mL/min/1.73m 且尿白蛋白与肌酐比值为 200-5000 mg/g（22.6-565 mg/mol）的患者被随机分配至达格列净 10mg 或安慰剂组，作为标准治疗的辅助治疗。主要复合终点为 eGFR 持续下降 50%或更多、终末期肾病或因肾脏疾病相关或心血管原因导致的死亡。在 270 例 IgA 肾病患者（254 例[94%]通过先前的活检得到证实）中，137 例被随机分配至达格列净组，133 例被分配至安慰剂组，中位随访时间为 2.1 年。总体而言，患者平均年龄为 51.2 岁；平均 eGFR 为 43.8 mL/min/1.73m；尿白蛋白与肌酐比值中位数为 900 mg/g。达格列净组有 6 例（4%）患者和安慰剂组有 20 例（15%）患者发生主要结局（风险比，0.29；95%置信区间，0.12，0.73）。达格列净组和安慰剂组的 eGFR 下降率分别为-3.5 和-4.7 mL/min/1.73m/年。与安慰剂相比，达格列净使尿白蛋白与肌酐比值降低了 26%。达格列净组和安慰剂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，且在该人群中未发现新的安全性发现。因此，在 IgA 肾病患者中，达格列净降低了慢性肾脏病进展的风险，且具有良好的安全性。
