皮质类固醇疗法与重症 COVID-19 患者急性肾损伤减少及中性粒细胞胞外诱捕网标志物降低的关联：一项观察性研究

Association of corticosteroid therapy with reduced acute kidney injury and lower NET markers in severe COVID-19: an observational study.

作者信息

Bülow Anderberg Sara, Huckriede Joram, Hultström Michael, Larsson Anders, de Vries Femke, Lipcsey Miklos, Nicolaes Gerry A F, Frithiof Robert

机构信息

Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, 751 85, Uppsala, Sweden.

Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, Netherlands.

出版信息

Intensive Care Med Exp. 2024 Sep 28;12(1):85. doi: 10.1186/s40635-024-00670-3.

DOI:10.1186/s40635-024-00670-3

PMID:39340756

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11438749/

Abstract

BACKGROUND

Acute kidney injury (AKI) is common in critical cases of coronavirus disease 2019 (COVID-19) and associated with worse outcome. Dysregulated neutrophil extracellular trap (NET) formation is one of several suggested pathophysiological mechanisms involved in the development of COVID-19 associated AKI. The corticosteroid dexamethasone was implemented as a standard treatment for severe COVID-19 as of June 2020. A sub-analysis of a prospective observational single center study was performed to evaluate the effect of corticosteroid treatment on AKI development and NET markers in critical cases of COVID-19.

RESULTS

Two hundred and ten adult patients admitted to intensive care at a tertiary level hospital due to respiratory failure or shock secondary to SARS-CoV-2-infection between March 13th 2020 and January 14th 2021 were included in the study. Ninety-seven of those did not receive corticosteroids. One hundred and thirteen patients were treated with corticosteroids [dexamethasone (n = 98) or equivalent treatment (n = 15)], but the incidence of AKI was assessed only in patients that received corticosteroids before any registered renal dysfunction (n = 63). Corticosteroids were associated with a lower incidence of AKI (19% vs 55.8%, p < 0.001). Fewer patients demonstrated detectable concentrations of extracellular histones in plasma when treated with corticosteroids (8.7% vs 43.1%; p < 0.001). Extracellular histones and in particular non-proteolyzed histones were observed more frequently with increasing AKI severity (p < 0.001). MPO-DNA was found in lower concentrations in patients that received corticosteroids before established renal dysfunction (p = 0.03) and was found in higher concentrations in patients with AKI stage 3 (p = 0.03). Corticosteroids did not ameliorate established AKI during the first week of treatment.

CONCLUSION

Corticosteroid treatment in severe COVID-19 is associated with a lower incidence of AKI and reduced concentrations of NET markers in plasma.

摘要

背景

急性肾损伤（AKI）在2019冠状病毒病（COVID-19）危重症中很常见，且与更差的预后相关。中性粒细胞胞外陷阱（NET）形成失调是COVID-19相关AKI发生发展中几种推测的病理生理机制之一。自2020年6月起，皮质类固醇地塞米松被用作重症COVID-19的标准治疗药物。进行了一项前瞻性观察性单中心研究的亚分析，以评估皮质类固醇治疗对COVID-19危重症患者AKI发生及NET标志物的影响。

结果

2020年3月13日至2021年1月14日期间，因严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染继发呼吸衰竭或休克而入住三级医院重症监护病房的210例成年患者纳入本研究。其中97例未接受皮质类固醇治疗。113例患者接受了皮质类固醇治疗[地塞米松（n = 98）或等效治疗（n = 15）]，但仅对在出现任何已登记的肾功能障碍之前接受皮质类固醇治疗的患者（n = 63）评估了AKI的发生率。皮质类固醇治疗与较低的AKI发生率相关（19%对55.8%，p < 0.001）。接受皮质类固醇治疗的患者血浆中可检测到细胞外组蛋白浓度的比例更低（8.7%对43.1%；p < 0.001）。随着AKI严重程度增加，细胞外组蛋白尤其是未被蛋白水解的组蛋白更常被观察到（p < 0.001）。在出现肾功能障碍之前接受皮质类固醇治疗的患者中，髓过氧化物酶-脱氧核糖核酸（MPO-DNA）浓度较低（p = 0.03），而在AKI 3期患者中浓度较高（p = 0.03）。在治疗的第一周，皮质类固醇并未改善已确诊的AKI。