Acute kidney injury due to COVID-19 and the circadian rhythm

Abstract

The COVID-19 pandemic caused by the novel coronavirus (SARS-CoV-2) affects several organs including the kidneys. When examining patients with acute kidney injury (AKI) due to COVID-19, it is important to consider the circadian rhythm because in addition to its biological clock function, disruption of the circadian rhythm has been reported to be associated with the pathogenesis of several disorders, including AKI. Angiotensin-converting enzyme 2 (ACE2), an important component of the renin-angiotensin-aldosterone system (RAAS), displays circadian rhythmicity. Studies have shown that over-expression of human ACE2 increases the replication of SARS-CoV-2, which may lead to disruptions and tissue damage due to the suppression of the brain and muscle ARNT-like protein-1(Bmal1) gene and high pro-inflammatory cytokines expressions in the tissues. Therefore, understanding and regulating the circadian rhythm and expression pattern of the key components of RAAS can prevent or reduce the severity of acute kidney injury that may occur with COVID-19 infection.

Keywords: Acute kidney injury; Bmal1; COVID-19; Circadian rhythm; Renin-angiotensin-aldosterone system.

Fig. 1

Disruption of the circadian rhythm results in a decrease in the expression of the Bmal1 gene which may trigger circadian disorders. Dysregulated renin-angiotensin-aldosterone system (RAAS) and the SARS-CoV-2 increase the level of Angiotensin II— which acts via AT₁ receptor to activate the NF-ĸB pathway and mediates inflammation in the kidneys by secreting pro-inflammatory cytokines.