Del Vecchio Lucia, Locatelli Francesco
Independent Researcher, Como, Italy.
Past Director, Department of Nephrology and Dialysis, Alessandro Manzoni Hospital, ASST Lecco, Lecco, Italy.
Clin Kidney J. 2020 Sep 2;13(4):494-499. doi: 10.1093/ckj/sfaa149. eCollection 2020 Aug.
Coronavirus disease 2019 (COVID-19) is a pandemic of unprecedented severity affecting millions of people around the world and causing several hundred thousands of deaths. The presentation of the disease ranges from asymptomatic manifestations through to acute respiratory distress syndrome with the necessity of mechanical ventilation. Cytokine storm and maladaptive responses to the viral spread in the body could be responsible for the severity of disease. Many patients develop acute kidney injury (AKI) during the course of their disease, especially in more severe cases. Many factors could cause kidney damage during infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is still unclear whether direct viral damage or the overexpression of cytokines and inflammatory factors are preeminent. According to autoptic studies, in most of the cases, AKI is due proximal tubular damage. However, cases of collapsing focal segmental glomerulosclerosis were reported as well in the absence of signs of direct viral infection of the kidney. Considering that severe hypoxia is a hallmark of severe SARS-CoV-2 infection, the involvement of the hypoxia-inducible factor (HIF) system is very likely, possibly influencing the inflammatory response and outcome in both the lungs and kidneys. Several bodies of evidence have shown a possible role of the HIF pathway during AKI in various kidney disease models. Similar observations were made in the setting of acute lung injury. In both organs, HIF activation by means of inhibition of the prolyl-hydroxylases domain (PHD) could be protective. Considering these promising experimental data, we hypothesize that PHD inhibitors could be considered as a possible new therapy against severe SARS-CoV-2 infection.
2019冠状病毒病（COVID-19）是一场前所未有的严重大流行，影响着全球数百万人，并导致数十万人死亡。该疾病的表现范围从无症状表现到需要机械通气的急性呼吸窘迫综合征。细胞因子风暴和机体对病毒传播的适应不良反应可能是疾病严重程度的原因。许多患者在患病过程中会发生急性肾损伤（AKI），尤其是在病情较重的情况下。在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染期间，许多因素可能导致肾脏损伤。目前尚不清楚直接的病毒损伤还是细胞因子和炎症因子的过度表达更为突出。根据尸检研究，在大多数情况下，急性肾损伤是由于近端肾小管损伤。然而，也有报道称出现了塌陷性局灶节段性肾小球硬化病例，而肾脏没有直接病毒感染的迹象。鉴于严重缺氧是严重SARS-CoV-2感染的一个标志，缺氧诱导因子（HIF）系统很可能参与其中，可能会影响肺部和肾脏的炎症反应及预后。有多项证据表明HIF途径在各种肾脏疾病模型的急性肾损伤中可能发挥作用。在急性肺损伤的情况下也有类似的观察结果。在这两个器官中，通过抑制脯氨酰羟化酶结构域（PHD）激活HIF可能具有保护作用。考虑到这些有前景的实验数据，我们推测PHD抑制剂可被视为一种针对严重SARS-CoV-2感染的可能新疗法。
