Oral antiviral therapies for COVID-19 in patients with advanced chronic kidney disease or kidney failure.
Oral antiviral therapies for COVID-19 in patients with advanced chronic kidney disease or kidney failure.
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针对晚期慢性肾病或肾衰竭患者的 COVID-19 口服抗病毒疗法。
DOI：
10.1093/ndt/gfad058
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Sise,MeghanE
中科院分区：
文献类型：
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作者：
Cho,WonkyungJ;Harden,Destiny;Moreno,Daiana;Dinulos,JamesE;Hanna,PaulE;Wang,Qiyu;Kim,ArthurY;Sise,MeghanE
截至2022年12月，超过6.51亿人被诊断出患有2019冠状病毒病（COVID-19）， 660万人死于COVID-19。慢性肾脏疾病（CKD）是COVID-19住院和死亡的重要独立危险因素[2,3]。尽管自引入有效疫苗以来病死率有所下降，但晚期CKD和需要肾脏替代治疗的肾衰竭患者仍然面临严重COVID-19后果的高风险；贝尔及其同事最近的一份报告发现，在完全接种疫苗的肾衰竭患者中，诊断出COVID-19后30天的死亡率为7%。在肾衰竭患者中，疫苗的有效性可能会减弱，并且单克隆疗法对当前的Omicron变体不再有效[5,6]。因此，迫切需要有效的抗病毒治疗来降低这一人群的发病率和死亡率。Nirmatrelvir/ritonavir和molnupiravir均于2021年12月获得美国食品和药物管理局（fda）的紧急使用授权（EUA）。晚期CKD[估计肾小球滤过率(eGFR)< 30 mL/min/1.73 m2]和肾衰竭患者被排除在导致这些药物获批的试验之外[7,8]。莫诺匹拉韦的EUA包括所有水平的eGFR，因为药代动力学研究表明，肾脏损害对药物水平的影响很小[10]；然而，它在晚期CKD和肾衰竭中的应用数据有限。相反，一项尼马特利韦/利托那韦的药代动力学研究表明，肾功能受损患者的药物暴露量明显增加，因此建议eGFR为30 - 59 mL/min/1.73 m2的患者剂量减少至150/100 mg，每日两次，eGFR< 30 mL/min/1.73 m2[9]的患者避免使用尼马特利韦/利托那韦。由于关于在eGFR< 30 mL/min/1.73 m2的患者中使用molnupiravir或nirmatrelvir/ritonavir的数据有限，我们试图在我们的医疗保健网络中描述实际使用情况。在一个为马萨诸塞州和新罕布什尔州150万患者提供护理的大型医疗保健系统中，我们确定了2022年1月至10月期间服用莫努匹拉韦或尼马特利韦/利托那韦的患者，在此期间，Omicron及其亚变体一直是美国bbb的主要菌株。我们纳入了在开始口服抗病毒治疗前eGFR< 30 mL/min/1.73 m2或肾衰竭的患者。我们将基线eGFR定义为在COVID-19诊断前14至365天之间所有eGFR测量的中位数。我们回顾了从开始日期到治疗完成后4周的所有临床文献，以确定潜在的不良事件（ae）。这项研究得到了麻省总院布里格姆机构审查委员会的批准；不再需要知情同意。
As of December 2022, over 651 million people have been diagnosed with coronavirus disease 2019 (COVID-19) and 6.6 million people have died of COVID-19 [1]. Chronic kidney disease (CKD) is an important independent risk factor for hospitalization and death due to COVID-19 [2, 3]. Although case fatality has decreased since the introduction of effective vaccines, patients with advanced CKD and kidney failure requiring kidney replacement therapy remain at high risk for severe COVID-19 outcomes; a recent report by Bell and colleagues found a 7% 30-day mortality risk after COVID-19 diagnosis in fully vaccinated patients with kidney failure [4]. Vaccine effectiveness may be attenuated in patients with kidney failure, and monoclonal therapies are no longer effective against current Omicron variants [5, 6]. Thus, there is a pressing need for effective antiviral therapies to decrease morbidity and mortality in this population. Nirmatrelvir/ritonavir and molnupiravir each received emergency use authorization (EUA) from the Food and Drug Administration in December 2021. Patients with advanced CKD [estimated glomerular filtration rate (eGFR)< 30 mL/min/1.73 m2] and kidney failure were excluded from the trials that led to the approval of these agents [7, 8]. The EUA for molnupiravir includes all levels of eGFR because pharmacokinetic studies demonstrated that kidney impairment had a small impact on drug levels [8]; however, there are limited data on its use in advanced CKD and kidney failure. In contrast, a pharmacokinetic study of nirmatrelvir/ritonavir demonstrated significantly higher drug exposures in patients with impaired kidney function which led to the recommendation that the dose be reduced to 150/100 mg twice daily for patients with eGFR 30–59 mL/min/1.73 m2, and that nirmatrelvir/ritonavir be avoided in patients with eGFR< 30 mL/min/1.73 m2 [9]. Because limited data exist on the use of either molnupiravir or nirmatrelvir/ritonavir in patients with eGFR< 30 mL/min/1.73 m2, we sought to characterize real-world use within our healthcare network.In a large healthcare system providing care for 1.5 million patients in Massachusetts and New Hampshire, we identified patients who were prescribed molnupiravir or nirmatrelvir/ritonavir between January and October 2022, during which Omicron and its subvariants have been the predominant strains in the USA [10]. We included those with eGFR< 30 mL/min/1.73 m2 or kidney failure before beginning oral antiviral therapy. We defined baseline eGFR as the median of all eGFR measurements between 14 and 365 days prior to diagnosis of COVID-19 [11]. We reviewed all clinical documentation between the start date and 4 weeks after therapy completion to identify potential adverse events (AEs). This study was approved by the Mass General Brigham Institutional Review Board; the need for informed consent was waived.