Overexpression of the SARS CoV 2 receptor, ACE 2, in diabetic kidney disease: implications for kidney injury in Covid 19

Abstract Objective Diabetes is associated with adverse outcomes including death following Covid-19 infection. Beyond the lungs, SARS-CoV-2, the aetiological agent of the Covid-19 pandemic, can infect a range of other tissues including the kidney, potentially contributing to the acute kidney injury in those with severe disease. We hypothesised that the renal abundance of ACE2, the cell surface receptor for SARS-CoV-2, may be modulated by diabetes and agents that block the renin-angiotensin-aldosterone system (RAAS). Methods The expression of ACE2 was examined in 49 archival kidney biopsies from patients with diabetic kidney disease and from 12 healthy, potential living allograft donors using next generation sequencing technology (RNA Seq). Results Mean ACE2 mRNA was increased approximately two-fold in diabetes when compared with healthy controls (13.2 ± 7.9 versus 7.7 ± 3.6 reads per million reads [RPM]; mean ± SD; diabetic versus controls; p = 0.001). No difference in transcript abundance was noted between recipients and non-recipients of agents that block the renin-angiotensin-aldosterone system (12.2 ± 6.7 versus 16.2 ± 10.7 RPM; RAAS recipients versus non-recipients; p=0.25). Conclusions Increased ACE2 mRNA in the diabetic kidney may increase the risk and/or severity of kidney infection with SARS-CoV-2 in the setting of Covid-19 disease. Further studies are needed to ascertain whether this diabetes-related overexpression is generalizable to other tissues, most notably the lungs.