Heerspink Hiddo J L, Furtado Remo H M, Berwanger Otavio, Koch Gary G, Martinez Felipe, Mukhtar Omar, Verma Subodh, Gasparyan Samvel B, Tang Fengming, Windsor Sheryl L, de Souza-Dantas Vicente Cés, Del Sueldo Mildren, Frankel Robert, Javaheri Ali, Maldonado Rafael A, Morse Caryn, Mota-Gomes Marco, Shemin Douglas, Silva Osvaldo Lourenço, Tognon Alexandre Pereira, Twahirwa Marcel, Buenconsejo Joan, Esterline Russell, Oscarsson Jan, Ambery Philip, Langkilde Anna Maria, Kosiborod Mikhail N
University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
The George Institute for Global Health, Newtown, NSW, Australia.
Clin J Am Soc Nephrol. 2022 May;17(5):643-654. doi: 10.2215/CJN.14231021. Epub 2022 Apr 28.
Patients who were hospitalized with coronavirus disease 2019 (COVID-19) infection are at high risk of AKI and KRT, especially in the presence of CKD. The Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial showed that in patients hospitalized with COVID-19, treatment with dapagliflozin versus placebo resulted in numerically fewer participants who experienced organ failure or death, although these differences were not statistically significant. We performed a secondary analysis of the DARE-19 trial to determine the efficacy and safety of dapagliflozin on kidney outcomes in the overall population and in prespecified subgroups of participants defined by baseline eGFR.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The DARE-19 trial randomized 1250 patients who were hospitalized (231 [18%] had eGFR <60 ml/min per 1.73 m) with COVID-19 and cardiometabolic risk factors to dapagliflozin or placebo. Dual primary outcomes (time to new or worsened organ dysfunction or death, and a hierarchical composite end point of recovery [change in clinical status by day 30]), and the key secondary kidney outcome (composite of AKI, KRT, or death), and safety were assessed in participants with baseline eGFR <60 and ≥60 ml/min per 1.73 m.
The effect of dapagliflozin versus placebo on the primary prevention outcome (hazard ratio, 0.80; 95% confidence interval, 0.58 to 1.10), primary recovery outcome (win ratio, 1.09; 95% confidence interval, 0.97 to 1.22), and the composite kidney outcome (hazard ratio, 0.74; 95% confidence interval, 0.50 to 1.07) were consistent across eGFR subgroups ( for interaction: 0.98, 0.67, and 0.44, respectively). The effects of dapagliflozin on AKI were also similar in participants with eGFR <60 ml/min per 1.73 m (hazard ratio, 0.71; 95% confidence interval, 0.29 to 1.77) and ≥60 ml/min per 1.73 m (hazard ratio, 0.69; 95% confidence interval, 0.37 to 1.29). Dapagliflozin was well tolerated in participants with eGFR <60 and ≥60 ml/min per 1.73 m.
The effects of dapagliflozin on primary and secondary outcomes in hospitalized participants with COVID-19 were consistent in those with eGFR below/above 60 ml/min per 1.73 m. Dapagliflozin was well tolerated and did not increase the risk of AKI in participants with eGFR below or above 60 ml/min per 1.73 m.
2019年冠状病毒病（COVID-19）感染住院患者发生急性肾损伤（AKI）和肾脏替代治疗（KRT）的风险很高，尤其是在存在慢性肾脏病（CKD）的情况下。COVID-19患者呼吸衰竭中使用达格列净（DARE-19）试验表明，在COVID-19住院患者中，与安慰剂相比，达格列净治疗导致发生器官衰竭或死亡的参与者在数量上更少，尽管这些差异无统计学意义。我们对DARE-19试验进行了二次分析，以确定达格列净在总体人群以及根据基线估算肾小球滤过率（eGFR）定义的预设亚组参与者中对肾脏结局的疗效和安全性。
设计、设置、参与者及测量指标：DARE-19试验将1250例因COVID-19和心血管代谢危险因素住院的患者（231例[18%]eGFR<60 ml/（min·1.73 m²））随机分为达格列净组或安慰剂组。在基线eGFR<60和≥60 ml/（min·1.73 m²）的参与者中评估双重主要结局（出现新的或恶化的器官功能障碍或死亡的时间，以及恢复的分层综合终点[第30天临床状态的变化]）、关键次要肾脏结局（AKI、KRT或死亡的综合）以及安全性。
达格列净与安慰剂相比，对主要预防结局（风险比，0.80；95%置信区间，0.58至1.10）、主要恢复结局（获胜比，1.09；95%置信区间，0.97至1.22）和综合肾脏结局（风险比，0.74；95%置信区间，0.50至1.07）在各eGFR亚组中是一致的（交互作用P值分别为0.98、0.67和0.44）。达格列净对AKI的影响在eGFR<60 ml/（min·1.73 m²）（风险比，0.71；95%置信区间，0.29至1.77）和≥60 ml/（min·1.73 m²）（风险比，0.69；95%置信区间，0.37至1.29）的参与者中也相似。达格列净在eGFR<60和≥60 ml/（min·1.73 m²）的参与者中耐受性良好。
达格列净对COVID-19住院参与者的主要和次要结局的影响在eGFR低于/高于60 ml/（min·1.73 m²）的患者中是一致的。达格列净耐受性良好，在eGFR低于或高于60 ml/（min·1.73 m²）的参与者中未增加AKI风险。
