Greater renal abundance of angiotensin-converting enzyme 2 (ACE2) in patients with diabetic kidney disease may increase their risk for kidney infection with SARS-CoV-2, the novel coronavirus that causes COVID-19, according to investigators.
SARS-CoV-2 enters cells by binding to ACE2 on cell surfaces. Beyond the lungs, the virus can infect a range of other organs, including the kidney, potentially contributing to acute kidney injury (AKI) in patients with severe COVID-19, investigators led by Richard E. Gilbert, MD, of St. Michael’s Hospital in Toronto, Ontario, Canada, explained in a paper published in the Canadian Journal of Diabetes.
Using next-generation sequencing technology to measure messenger RNA (mRNA), Dr Gilbert and his collaborators analyzed ACE2 expression in 49 archival kidney biopsy tissue specimens from patients with diabetic kidney disease and 12 healthy potential living kidney donors.
Mean ACE2 mRNA was increased approximately 2-fold in the diabetic kidneys compared with healthy controls (mean 13.2 vs 7.7 reads per million reads [RPM]), Dr Gilbert’s team reported. They observed no significant difference in transcript abundance between individuals on medications that block the renin-angiotensin-aldosterone system (RAAS) and those not receiving the medications (12.2 vs 16.2 RPM).
“An increase in ACE2 expression in the setting of diabetic kidney disease raises the possibility that such individuals may be at higher risk [for] kidney infection with SARS-CoV-2 in Covid-19 disease, potentially increasing the risk of AKI and death,” Dr Gilbert’s team concluded. “The study, further, provides reassurance that any propensity to infection should not be exacerbated by concomitant use of agents that block the RAAS.”
The authors acknowledged limitations of their study, notably that it was confined to the examination of kidney tissue, not lungs, which are the principal sites of COVID-19 infection. In addition, the investigators noted that they were unable to make any inferences as to whether the changes in ACE2 mRNA they observed in diabetic kidney tissue apply to other organs, most notably the lungs, or if the changes in ACE2 expression they observed also applies to kidneys of patients who have diabetes but normal kidney function.
Gilbert RE, Caldwell L, Misra PS, et al. Overexpression of the SARS-CoV-2 receptor, ACE-2, in diabetic kidney disease: implications for kidney injury in Covid-19 [published online July 18, 2020]. Can J Diabetes. doi: 10.1016/j.jcjd.2020.07.003