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

Abstract

Aims Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)—the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. Methods and results 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 characterized 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. Conclusion Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. 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.

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

“…In 221 hypertensive patients, no association between the use of βARBs and renal ACE2 gene expression was found (X. Jiang et al, 2020 ). In the context of COVID-19, a recent study with 880 COVID-19 patients reported that the use of βARBs was associated with a significantly better outcome ( Pinto-Sietsma et al, 2020 ).…”

“…or ARBs and renal ACE2 gene expression was found (X. Jiang et al, 2020 ). In addition, in kidney biopsies from 49 diabetic patients, treatment with ARBs and ACE-Inhs.…”

Pathogenesis of Acute Kidney Injury in Coronavirus Disease 2019

“…There is no correlation between ACE-Is/ARBs and AKI. Meanwhile, neither of them can increase the expression of ACE2 in the human kidney ( Jiang et al, 2020 ; Tetlow et al, 2020 ). CD147, also named EMMPRIN, is involved in tumor development, plasmodium invasion and virus infection ( Castro et al, 2003 ; Chen et al, 2005 ; Lu et al, 2018 ).…”

Renin-angiotensin system inhibitors in hospitalised patients with COVID-19

“…The irony is, that alongside these RCTs, we have also discovered that the COVID-19 RAS-inhibition controversy was most likely ill-founded in the first place, as recent data suggest that these drugs do not seem to increase ACE2 expression, especially in the lung, after all. 10 , 11 …”