Angiotensin-Converting Enzyme 2 and Urine Amino Acid Excretion Increase in COVID-19 Patients With AKI

ABSTRACT

Background: Angiotensin-converting enzyme 2(ACE2), the receptor for SARSCoV-2, is highly expressed in the kidneys. ACE2 also possess a unique function to facilitate amino acid absorption. A persistent elevation in plasma ACE2 during COVID-19 is related to increased mortality. The present study sought to explore the relationship between urine ACE2(uACE2) and renal outcomes in COVID-19 patients. Method(s) In 104 COVID-19 patients without acute kidney injury(AKI), 43 patients with COVID-19-mediated AKI, and 36 non-COVID-19 controls, uACE2, urine tumor necrosis factor receptors I and II(uTNF-RI and uTNF-RII), neutrophil gelatinaseassociated lipocalin(uNGAL), and urine albumin-creatinine ratio were measured. We also assessed ACE2 staining in autopsy kidney samples and generated a propensityscore matched subgroup to perform a targeted urine metabolomic study to describe the characteristic urine signature of COVID-19. Result(s) uACE2 was increased in patients with COVID-19, and further increased in those that developed AKI(Figure 1). After adjusting uACE2 levels for age, sex and previous comorbidities, increased uACE2 was independently associated with over 3-fold higher risk(OR 3.05,95%CI1.23-7.58, p=0.017) of developing AKI. Increased uACE2 corresponded to a tubular loss of ACE2 in kidney sections and strongly correlated with uTNF-RI and uTNF-RII, suggesting that ADAM17 could be responsible for ACE2 shedding. Urine quantitative metabolome analysis revealed an increased excretion of essential amino acids in COVID-19 patients, including leucine, isoleucine, tryptophan and phenylalanine. Additionally, a strong correlation was observed between urine amino acids and uACE2(Figure 1). Conclusion(s) Elevated uACE2 is related to AKI in patients with COVID-19. The loss of tubular ACE2 during SARS-CoV-2 infection demonstrates a potential link between aminoaciduria and proximal tubular injury.