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COVID-19 患者肾移植受者中托珠单抗的应用。

Use of tocilizumab in kidney transplant recipients with COVID-19.

机构信息

Department of Nephrology, Hospital del Mar, Institute Mar for Medical Research, REDinREN (RD16/0009/0013), Barcelona, Spain.

Department of Nephrology and Kidney, Transplantation Hospital Clinic, Institute of Biomedical Research August Pi i Sunyer, REDinREN (RD16/0009/0023), Barcelona, Spain.

出版信息

Am J Transplant. 2020 Nov;20(11):3182-3190. doi: 10.1111/ajt.16192. Epub 2020 Aug 4.

Abstract

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.

摘要

与冠状病毒感染相关的急性呼吸窘迫综合征与细胞因子风暴有关,大量白细胞介素-6(IL-6)释放。IL-6 受体阻滞剂托珠单抗可能控制 2019 年冠状病毒病(COVID-19)患者的异常宿主免疫反应。在这场大流行中,肾移植(KT)受者是严重感染的高危人群,预后较差。我们报告了一项多中心队列研究,该研究纳入了 80 例在住院期间接受托珠单抗治疗的严重 COVID-19 KT 患者。研究发现死亡率较高(32.5%),与年龄较大有关(年龄超过 60 岁的患者危险比 [HR] 为 3.12,P=0.039)。IL-6 和其他炎症标志物,包括乳酸脱氢酶、铁蛋白和 D-二聚体,在托珠单抗给药后早期升高,且在非幸存者中更高。相反,CRP 水平在托珠单抗后下降,并且这种下降与生存呈正相关(幸存者为 12.3mg/L,非幸存者为 33mg/L)。托珠单抗后 CRP 每增加 1mg/L,死亡风险增加 1%(HR 1.01 [置信区间 1.004-1.024],P=0.003)。尽管死亡患者入院时的呼吸状况较差,但在托珠单抗给药时并无显著差异,并且在多变量分析中对结局无影响。托珠单抗可能在控制 COVID-19 中的细胞因子风暴方面有效,但需要随机试验。

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