Hypertension and renin-angiotensin system blockers are not associated with expression of Angiotensin Converting Enzyme 2 (ACE2) in the kidney

Abstract

Angiotensin converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2) - the cause of COVID-19 disease. It has been hypothesized that use of renin-angiotensin system (RAS) inhibiting medications in patients with hypertension, increases the expression of ACE2 and thereby increases the risk of COVID-19 infection and severe outcomes or death. However, the effect of RAS-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. We examined how hypertension, its major metabolic co-phenotypes and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterised by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. Collectively, our data indicate that neither hypertension nor antihypertensive treatment are likely to alter individual risk of SARS-CoV-2 infection or influence clinical outcomes in COVID-19 through changes of ACE2 expression. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.

Renin Angiotensin System Inhibition and Susceptibility and Outcomes from COVID-19: A Systematic Review and Meta-analysis of 69,200 COVID-19 Patients

“…Whilst circulating ACE2 may not be a good indicator of tissue ACE2 levels, other recent evidence suggests that there is increasing expression of ACE2 with age in both human lungs and kidney but no association between the expression of ACE2 with either hypertension or RAS inhibiting drugs. 12 Thus, the hypothesis that RAS inhibitors could increase risk from COVID-19 by increasing ACE2 expression is unsupported by the limited pathophysiological data available, or the more extensive clinical data from the cohort studies of patients included in this meta-analysis. This in turn, reinforces the recommendations made by medical societies, for patients to continue with their RAS inhibitor medications throughout this COVID-19 pandemic.…”