Clin Kidney J . Hypoxia response and acute lung and kidney injury: possible implications for therapy of COVID-19

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Clin Kidney J


. 2020 Sep 2;13(4):494-499.
doi: 10.1093/ckj/sfaa149. eCollection 2020 Aug.
Hypoxia response and acute lung and kidney injury: possible implications for therapy of COVID-19


Lucia Del Vecchio ¹ , Francesco Locatelli ²



Affiliations

• PMID: 32905208
• PMCID: PMC7467604
• DOI: 10.1093/ckj/sfaa149

Abstract

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.

Keywords: COVID-19; PHD inhibitors; SARS-CoV-2; acute kidney injury; acute lung injury; focal segmental glomerulonephritis; hypoxia; hypoxia-inducible factor.