Abstract
The coronavirus 2019 (COVID-19) pandemic has caused a huge impact on health and economic issues. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes cellular damage by entry mediated by the angiotensin-converting enzyme 2 of the host cells and its conjugation with spike proteins of SARS-CoV-2. Beyond airway infection and acute respiratory distress syndrome, acute kidney injury is common in SARS-CoV-2-associated infection, and acute kidney injury (AKI) is predictive to multiorgan dysfunction in SARS-CoV-2 infection. Beyond the cytokine storm and hemodynamic instability, SARS-CoV-2 might directly induce kidney injury and cause histopathologic characteristics, including acute tubular necrosis, podocytopathy and microangiopathy. The expression of apparatus mediating SARS-CoV-2 entry, including angiotensin-converting enzyme 2, transmembrane protease serine 2 (TMPRSS2) and a disintegrin and metalloprotease 17 (ADAM17), within the renal tubular cells is highly associated with acute kidney injury mediated by SARS-CoV-2. Both entry from the luminal and basolateral sides of the renal tubular cells are the possible routes for COVID-19, and the microthrombi associated with severe sepsis and the dysregulated renin–angiotensin–aldosterone system worsen further renal injury in SARS-CoV-2-associated AKI. In the podocytes of the glomerulus, injured podocyte expressed CD147, which mediated the entry of SARS-CoV-2 and worsen further foot process effacement, which would worsen proteinuria, and the chronic hazard induced by SARS-CoV-2-mediated kidney injury is still unknown. Therefore, the aim of the review is to summarize current evidence on SARS-CoV-2-associated AKI and the possible pathogenesis directly by SARS-CoV-2.
Highlights
The coronavirus disease 2019 (COVID-19) pandemic has had severe public health and economic impacts as a result of its rapid spread and association with severe acute respiratory distress syndrome
This review investigated the possible molecular mechanisms of acute kidney injury directly mediated by SARS-CoV-2
The mechanisms of Acute kidney injury (AKI) induced by SARS-CoV-2 involve hemodynamic factors, direct cellular injury caused by SARS-CoV-2 invasion through Angiotensin-converting enzyme 2 (ACE2) or the cytokine storm induced by SARS-CoV-2, because the SARS-CoV-2 could not be detected in the postmortem autopsy or in the graft of renal transplantation patients when using RNA in-situ hybridization or by immunochemistry for nucleocapsid [47,48,49]
Summary
The coronavirus disease 2019 (COVID-19) pandemic has had severe public health and economic impacts as a result of its rapid spread and association with severe acute respiratory distress syndrome. Studies have reported high levels of ACE2 and TMPRSS2 expression in proximal renal tubular epithelial cells and kidney podocytes [10,11,12], and such characteristics facilitate the SARS-CoV replication within these cells [13]. In SARS-CoV-2, this occurs as a result of the spike protein activating ACE2 expression by seizing two host proteases: TMPRSS2, which facilitates viral entry by cleaving the S antigen into S1 (the active binding site), and ADAM17, which downregulates ACE2 expression by shedding ACE2 proteins into soluble form. In the human embryonic kidney cell line, decreased ACE2 expression is responsible for SARS-CoV-2 complications and end-organ damage and may cause greater harm to the host through enhanced ACE2 toxic effects, such as the activation of proinflammatory cytokines [22]. More studies are necessary to clarify the role of ADAM17 and other proteases on ACE2 shedding in the kidney and the importance of these proteases in SARS-CoV-2 infection [27]
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