{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:40:39Z","timestamp":1740138039930,"version":"3.37.3"},"reference-count":93,"publisher":"Portland Press Ltd.","issue":"21","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,11,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Angiotensin-converting enzyme II (ACE2) is a homologue of angiotensin-converting enzyme discovered in 2000. From the initial discovery, it was recognized that the kidneys were organs very rich on ACE2. Subsequent studies demonstrated the precise localization of ACE2 within the kidney and the importance of this enzyme in the metabolism of Angiotensin II and the formation of Angiotensin 1\u20137. With the recognition early in 2020 of ACE2 being the main receptor of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), the interest in this protein has dramatically increased. In this review, we will focus on kidney ACE2; its localization, its alterations in hypertension, diabetes, the effect of ACE inhibitors and angiotensin type 1 receptor blockers (ARBs) on ACE2 and the potential use of ACE2 recombinant proteins therapeutically for kidney disease.<\/jats:p>\n               <jats:p>We also describe the emerging kidney manifestations of COVID-19, namely the frequent development of acute kidney injury. The possibility that binding of SARS-CoV-2 to kidney ACE2 plays a role in the kidney manifestations is also briefly discussed.<\/jats:p>","DOI":"10.1042\/cs20200484","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T08:51:05Z","timestamp":1604307065000},"page":"2791-2805","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["ACE2, the kidney and the emergence of COVID-19 two decades after ACE2 discovery"],"prefix":"10.1042","volume":"134","author":[{"given":"Enrique","family":"Lores","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Wysocki","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5878-9046","authenticated-orcid":false,"given":"Daniel","family":"Batlle","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"2021113011170459100_B1","doi-asserted-by":"publisher","first-page":"33238","DOI":"10.1074\/jbc.M002615200","article-title":"A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase","volume":"275","author":"Tipnis","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2021113011170459100_B2","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1161\/01.RES.87.5.e1","article-title":"A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9","volume":"87","author":"Donoghue","year":"2000","journal-title":"Circ. Res."},{"key":"2021113011170459100_B3","doi-asserted-by":"publisher","first-page":"14838","DOI":"10.1074\/jbc.M200581200","article-title":"Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase","volume":"277","author":"Vickers","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2021113011170459100_B4","doi-asserted-by":"publisher","first-page":"13185","DOI":"10.1021\/bi035268s","article-title":"Angiotensin-converting enzyme-2 (ACE2): comparative modeling of the active site, specificity requirements, and chloride dependence","volume":"42","author":"Guy","year":"2003","journal-title":"Biochemistry"},{"key":"2021113011170459100_B5","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1042\/BJ20040634","article-title":"Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism","volume":"383","author":"Rice","year":"2004","journal-title":"Biochem. J."},{"key":"2021113011170459100_B6","first-page":"273","article-title":"Apelin and ACE2 in cardiovascular disease","volume":"11","author":"Kalea","year":"2010","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"2021113011170459100_B7","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1002\/path.1570","article-title":"Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis","volume":"203","author":"Hamming","year":"2004","journal-title":"J. Pathol.: J. Pathological Soc. Great Britain and Ireland."},{"key":"2021113011170459100_B8","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/nature03712","article-title":"Angiotensin-converting enzyme 2 protects from severe acute lung failure","volume":"436","author":"Imai","year":"2005","journal-title":"Nature"},{"key":"2021113011170459100_B9","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1136\/gut.2004.062398","article-title":"Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2","volume":"54","author":"Paizis","year":"2005","journal-title":"Gut"},{"key":"2021113011170459100_B10","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.placenta.2005.02.015","article-title":"Distribution of angiotensin-(1-7) and ACE2 in human placentas of normal and pathological pregnancies","volume":"27","author":"Valdes","year":"2006","journal-title":"Placenta"},{"key":"2021113011170459100_B11","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1161\/01.HYP.30.3.535","article-title":"Counterregulatory actions of angiotensin-(1-7)","volume":"30","author":"Ferrario","year":"1997","journal-title":"Hypertension"},{"key":"2021113011170459100_B12","doi-asserted-by":"publisher","first-page":"8258","DOI":"10.1073\/pnas.1432869100","article-title":"Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas","volume":"100","author":"Santos","year":"2003","journal-title":"Proc. Natl. Acad. Sci."},{"key":"2021113011170459100_B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/path.2162","article-title":"The emerging role of ACE2 in physiology and disease","volume":"212","author":"Hamming","year":"2007","journal-title":"J. Pathol.: J. Pathological Soc. Great Britain and Ireland"},{"key":"2021113011170459100_B14","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.bbapap.2004.10.010","article-title":"Membrane-associated zinc peptidase families: comparing ACE and ACE2","volume":"1751","author":"Guy","year":"2005","journal-title":"Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics"},{"key":"2021113011170459100_B15","doi-asserted-by":"publisher","first-page":"H1013","DOI":"10.1152\/ajpheart.00068.2005","article-title":"Angiotensin II AT1 receptors regulate ACE2 and angiotensin-(1-7) expression in the aorta of spontaneously hypertensive rats","volume":"289","author":"Igase","year":"2005","journal-title":"Am. J. Physiol.-Heart and Circulatory Physiol."},{"key":"2021113011170459100_B16","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1038\/nature00786","article-title":"Angiotensin-converting enzyme 2 is an essential regulator of heart function","volume":"417","author":"Crackower","year":"2002","journal-title":"Nature"},{"key":"2021113011170459100_B17","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/S1050-1738(02)00233-5","article-title":"The role of ACE2 in cardiovascular physiology","volume":"13","author":"Oudit","year":"2003","journal-title":"Trends Cardiovasc. Med."},{"key":"2021113011170459100_B18","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1113\/expphysiol.2005.031096","article-title":"Protection from angiotensin II-induced cardiac hypertrophy and fibrosis by systemic lentiviral delivery of ACE2 in rats","volume":"90","author":"Huentelman","year":"2005","journal-title":"Exp. Physiol."},{"key":"2021113011170459100_B19","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/nature02145","article-title":"Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus","volume":"426","author":"Li","year":"2003","journal-title":"Nature"},{"key":"2021113011170459100_B20","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1093\/eurheartj\/ehi114","article-title":"Myocardial infarction increases ACE2 expression in rat and humans","volume":"26","author":"Burrell","year":"2005","journal-title":"Eur. Heart J."},{"key":"2021113011170459100_B21","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.tem.2004.03.001","article-title":"ACE2, a new regulator of the renin\u2013angiotensin system","volume":"15","author":"Burrell","year":"2004","journal-title":"Trends in Endocrinol. Metab."},{"key":"2021113011170459100_B22","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1038\/nm1267","article-title":"A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus\u2013induced lung injury","volume":"11","author":"Kuba","year":"2005","journal-title":"Nat. Med."},{"key":"2021113011170459100_B23","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1161\/01.HYP.0000126192.27644.76","article-title":"Increased ACE 2 and decreased ACE protein in renal tubules from diabetic mice: a renoprotective combination?","volume":"43","author":"Ye","year":"2004","journal-title":"Hypertension"},{"key":"2021113011170459100_B24","doi-asserted-by":"publisher","first-page":"3067","DOI":"10.1681\/ASN.2006050423","article-title":"Glomerular localization and expression of angiotensin-converting enzyme 2 and angiotensin-converting enzyme: implications for albuminuria in diabetes","volume":"17","author":"Ye","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"2021113011170459100_B25","doi-asserted-by":"publisher","first-page":"F398","DOI":"10.1152\/ajprenal.90488.2008","article-title":"Localization of ACE2 in the renal vasculature: amplification by angiotensin II type 1 receptor blockade using telmisartan","volume":"296","author":"Soler","year":"2009","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"2021113011170459100_B26","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1161\/HYPERTENSIONAHA.109.138420","article-title":"Targeting the degradation of angiotensin II with recombinant angiotensin-converting enzyme 2: prevention of angiotensin II\u2013dependent hypertension","volume":"55","author":"Wysocki","year":"2010","journal-title":"Hypertension"},{"key":"2021113011170459100_B27","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1038\/ki.2011.381","article-title":"Angiotensin-converting enzyme 2: enhancing the degradation of angiotensin II as a potential therapy for diabetic nephropathy","volume":"81","author":"Batlle","year":"2012","journal-title":"Kidney Int."},{"key":"2021113011170459100_B28","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1530\/JOE-12-0341","article-title":"Angiotensin-converting enzyme 2, angiotensin-(1-7) and Mas: new players of the renin-angiotensin system","volume":"216","author":"Santos","year":"2013","journal-title":"J. Endocrinol."},{"key":"2021113011170459100_B29","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2009.70","article-title":"Angiotensin-(1-7) and its effects in the kidney","volume":"9","author":"Dilauro","year":"2009","journal-title":"Scientific World J."},{"key":"2021113011170459100_B30","first-page":"e13513","article-title":"An update on ACE2 amplification and its therapeutic potential","volume":"2020","author":"Marquez","journal-title":"Acta Physiol (Oxf)"},{"key":"2021113011170459100_B31","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.15256","article-title":"The interaction of SARS-CoV-2 and other coronavirus with Angiotensin Converting Enzyme 2 (ACE2) as their main receptor: therapeutic implications","author":"Davidson","year":"2020","journal-title":"Hypertension"},{"key":"2021113011170459100_B32","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1161\/HYPERTENSIONAHA.119.14071","article-title":"Ang II (Angiotensin II) Conversion to Angiotensin-(1-7) in the Circulation Is POP (Prolyloligopeptidase)-Dependent and ACE2 (Angiotensin-Converting Enzyme 2)-Independent","volume":"75","author":"Serfozo","year":"2020","journal-title":"Hypertension"},{"key":"2021113011170459100_B33","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/s41586-020-2180-5","article-title":"Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor","volume":"581","author":"Lan","year":"2020","journal-title":"Nature"},{"key":"2021113011170459100_B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"2021113011170459100_B35","article-title":"Structural and functional basis of SARS-CoV-2 entry by using human ACE2","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"2021113011170459100_B36","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1161\/CIRCRESAHA.120.317015","article-title":"Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2","volume":"126","author":"Gheblawi","year":"2020","journal-title":"Circ. Res."},{"key":"2021113011170459100_B37","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1042\/CS20200163","article-title":"Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy?","volume":"134","author":"Batlle","year":"2020","journal-title":"Clin. Sci."},{"key":"2021113011170459100_B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.004","article-title":"Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2","author":"Monteil","year":"2020","journal-title":"Cell"},{"key":"2021113011170459100_B39","doi-asserted-by":"publisher","first-page":"2132","DOI":"10.2337\/db06-0033","article-title":"ACE and ACE2 activity in diabetic mice","volume":"55","author":"Wysocki","year":"2006","journal-title":"Diabetes"},{"key":"2021113011170459100_B40","doi-asserted-by":"publisher","first-page":"39353","DOI":"10.1074\/jbc.M508914200","article-title":"Angiotensin-converting enzyme 2 (ACE2), but not ACE, is preferentially localized to the apical surface of polarized kidney cells","volume":"280","author":"Warner","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2021113011170459100_B41","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1002\/path.1670","article-title":"Renal ACE2 expression in human kidney disease","volume":"204","author":"Lely","year":"2004","journal-title":"J. Pathol.: J. Pathological Soc. Great Britain and Ireland"},{"key":"2021113011170459100_B42","doi-asserted-by":"publisher","first-page":"1016e19","DOI":"10.1016\/j.cell.2020.04.035","article-title":"SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues","volume":"181","author":"Ziegler","year":"2020","journal-title":"Cell"},{"key":"2021113011170459100_B43","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1161\/01.HYP.0000060689.38912.CB","article-title":"Characterization of renal angiotensin-converting enzyme 2 in diabetic nephropathy","volume":"41","author":"Tikellis","year":"2003","journal-title":"Hypertension"},{"key":"2021113011170459100_B44","doi-asserted-by":"publisher","first-page":"F353","DOI":"10.1152\/ajprenal.00144.2004","article-title":"The role of angiotensin converting enzyme 2 in the generation of angiotensin 1-7 by rat proximal tubules","volume":"288","author":"Li","year":"2005","journal-title":"Am. J. Physiol.-Renal Physiol."},{"key":"2021113011170459100_B45","doi-asserted-by":"publisher","first-page":"F398","DOI":"10.1152\/ajprenal.00050.2007","article-title":"Characterization of renin-angiotensin system enzyme activities in cultured mouse podocytes","volume":"293","author":"Velez","year":"2007","journal-title":"Am. J. Physiol.-Renal Physiol."},{"key":"2021113011170459100_B46","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020040419","article-title":"Acute kidney injury in COVID-19: emerging evidence of a distinct pathophysiology","author":"Batlle","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"2021113011170459100_B47","first-page":"1","article-title":"Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection","author":"Zou","year":"2020","journal-title":"Front. Med."},{"key":"2021113011170459100_B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.04.003","article-title":"Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China","author":"Su","year":"2020","journal-title":"Kidney Int."},{"key":"2021113011170459100_B49","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2011400","article-title":"Multiorgan and renal tropism of SARS-CoV-2","author":"Puelles","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"2021113011170459100_B50","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1161\/01.HYP.0000146400.57221.74","article-title":"Upregulation of angiotensin-converting enzyme 2 by all-trans retinoic acid in spontaneously hypertensive rats","volume":"44","author":"Zhong","year":"2004","journal-title":"Hypertension"},{"key":"2021113011170459100_B51","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/sj.ki.5000428","article-title":"Developmental expression of ACE2 in the SHR kidney: a role in hypertension?","volume":"70","author":"Tikellis","year":"2006","journal-title":"Kidney Int."},{"key":"2021113011170459100_B52","doi-asserted-by":"publisher","first-page":"F749","DOI":"10.1152\/ajprenal.00383.2009","article-title":"Reciprocal changes in renal ACE\/ANG II and ACE2\/ANG 1-7 are associated with enhanced collecting duct renin in Goldblatt hypertensive rats","volume":"300","author":"Prieto","year":"2011","journal-title":"Am. J. Physiol.-Renal Physiol."},{"key":"2021113011170459100_B53","doi-asserted-by":"publisher","first-page":"2218","DOI":"10.1172\/JCI16980","article-title":"Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice","volume":"116","author":"Gurley","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2021113011170459100_B54","doi-asserted-by":"publisher","first-page":"e00264","DOI":"10.1002\/phy2.264","article-title":"ACE 2 deficiency increases NADPH-mediated oxidative stress in the kidney","volume":"2","author":"Wysocki","year":"2014","journal-title":"Physiol. Rep."},{"key":"2021113011170459100_B55","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1161\/HYPERTENSIONAHA.112.198622","article-title":"Murine recombinant angiotensin-converting enzyme 2: effect on angiotensin II-dependent hypertension and distinctive angiotensin-converting enzyme 2 inhibitor characteristics on rodent and human angiotensin-converting enzyme 2","volume":"60","author":"Ye","year":"2012","journal-title":"Hypertension"},{"key":"2021113011170459100_B56","doi-asserted-by":"publisher","DOI":"10.3390\/biom9120886","article-title":"Novel Variants of Angiotensin Converting Enzyme-2 of Shorter Molecular Size to Target the Kidney Renin Angiotensin System","volume":"9","author":"Wysocki","year":"2019","journal-title":"Biomolecules"},{"key":"2021113011170459100_B57","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1038\/sj.ki.5002373","article-title":"ACE2 inhibition worsens glomerular injury in association with increased ACE expression in streptozotocin-induced diabetic mice","volume":"72","author":"Soler","year":"2007","journal-title":"Kidney Int."},{"key":"2021113011170459100_B58","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1053\/j.ajkd.2007.11.022","article-title":"Expression of ACE and ACE2 in individuals with diabetic kidney disease and healthy controls","volume":"51","author":"Mizuiri","year":"2008","journal-title":"Am. J. Kidney Dis."},{"key":"2021113011170459100_B59","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1038\/ki.2008.497","article-title":"Decreased glomerular and tubular expression of ACE2 in patients with type 2 diabetes and kidney disease","volume":"74","author":"Reich","year":"2008","journal-title":"Kidney Int."},{"key":"2021113011170459100_B60","article-title":"Overexpression of the SARS-CoV-2 receptor, ACE-2, in diabetic kidney disease: implications for kidney injury in Covid-19","author":"Gilbert","year":"2020","journal-title":"Canadian J. Diab."},{"key":"2021113011170459100_B61","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1042\/CS20090318","article-title":"Reduction in renal ACE2 expression in subtotal nephrectomy in rats is ameliorated with ACE inhibition","volume":"118","author":"Velkoska","year":"2010","journal-title":"Clin. Sci."},{"key":"2021113011170459100_B62","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1113\/expphysiol.2011.063156","article-title":"Chronic kidney disease: cardiac and renal angiotensin-converting enzyme (ACE) 2 expression in rats after subtotal nephrectomy and the effect of ACE inhibition","volume":"97","author":"Burrell","year":"2012","journal-title":"Exp. Physiol."},{"key":"2021113011170459100_B63","doi-asserted-by":"publisher","first-page":"F1523","DOI":"10.1152\/ajprenal.00426.2009","article-title":"Effect of ACE2 and angiotensin-(1-7) in a mouse model of early chronic kidney disease","volume":"298","author":"Dilauro","year":"2010","journal-title":"Am. J. Physiol.-Renal Physiol."},{"key":"2021113011170459100_B64","article-title":"A novel short ACE2 variant causes ACE suppression and fosters Ang 1-7 formation in a murine model of CKD","author":"Gvantca Gulua","year":"2020","journal-title":"Am. Soc. Nephrol. Abstract"},{"key":"2021113011170459100_B65","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.15082","article-title":"Renin-Angiotensin System Blockers and the COVID-19 Pandemic: At Present There Is No Evidence to Abandon Renin-Angiotensin System Blockers","author":"Danser","year":"2020","journal-title":"Hypertension"},{"key":"2021113011170459100_B66","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsr2005760","article-title":"Renin\u2013angiotensin\u2013aldosterone system inhibitors in patients with Covid-19","author":"Vaduganathan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"2021113011170459100_B67","doi-asserted-by":"publisher","first-page":"2605","DOI":"10.1161\/CIRCULATIONAHA.104.510461","article-title":"Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2","volume":"111","author":"Ferrario","year":"2005","journal-title":"Circulation"},{"key":"2021113011170459100_B68","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30116-8","article-title":"Are patients with hypertension and diabetes mellitus at increased risk for Covid-19 infection?","author":"Fang","year":"2020","journal-title":"Lancet Respir Med"},{"key":"2021113011170459100_B69","doi-asserted-by":"publisher","first-page":"e21","DOI":"10.1016\/S2213-2600(20)30116-8","article-title":"Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?","volume":"8","author":"Fang","year":"2020","journal-title":"The Lancet Respiratory Med."},{"key":"2021113011170459100_B70","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020050667","article-title":"Kidney and Lung ACE2 Expression after an ACE Inhibitor or an Ang II Receptor Blocker: Implications for COVID-19","author":"Wysocki","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"2021113011170459100_B71","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00409.2004","article-title":"Distinct roles for ANG II and ANG-(1-7) in the regulation of angiotensin-converting enzyme 2 in rat astrocytes","author":"Gallagher","year":"2006","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"2021113011170459100_B72","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/ki.2012.83","article-title":"Podocyte-specific overexpression of human angiotensin-converting enzyme 2 attenuates diabetic nephropathy in mice","volume":"82","author":"Nadarajah","year":"2012","journal-title":"Kidney Int."},{"key":"2021113011170459100_B73","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1016\/j.kint.2016.09.032","article-title":"Angiotensin-converting enzyme 2 amplification limited to the circulation does not protect mice from development of diabetic nephropathy","volume":"91","author":"Wysocki","year":"2017","journal-title":"Kidney Int."},{"key":"2021113011170459100_B74","doi-asserted-by":"publisher","first-page":"F600","DOI":"10.1152\/ajprenal.00600.2012","article-title":"Regulation of urinary ACE2 in diabetic mice","volume":"305","author":"Wysocki","year":"2013","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"2021113011170459100_B75","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1016\/j.kint.2017.04.001","article-title":"ACE2 as therapy for glomerular disease: the devil is in the detail","volume":"91","author":"Ross","year":"2017","journal-title":"Kidney Int."},{"key":"2021113011170459100_B76","doi-asserted-by":"publisher","first-page":"428950","DOI":"10.1155\/2012\/428950","article-title":"Recombinant Expression and Characterization of Human and Murine ACE2: Species-Specific Activation of the Alternative Renin-Angiotensin-System","volume":"2012","author":"Poglitsch","year":"2012","journal-title":"Int. J. Hypertension"},{"key":"2021113011170459100_B77","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1016\/j.kint.2016.12.022","article-title":"Murine recombinant angiotensin-converting enzyme 2 attenuates kidney injury in experimental Alport syndrome","volume":"91","author":"Bae","year":"2017","journal-title":"Kidney Int."},{"key":"2021113011170459100_B78","doi-asserted-by":"publisher","first-page":"F487","DOI":"10.1152\/ajprenal.00074.2017","article-title":"Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease","volume":"313","author":"Wysocki","year":"2017","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"2021113011170459100_B79","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1038\/sj.ki.5000272","article-title":"Characterization of proteinuria and tubular protein uptake in a new model of oral L-lysine administration in rats","volume":"69","author":"Thelle","year":"2006","journal-title":"Kidney Int."},{"key":"2021113011170459100_B80","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1161\/HYPERTENSIONAHA.119.12873","article-title":"Urinary Renin in Patients and Mice With Diabetic Kidney Disease","volume":"74","author":"Tang","year":"2019","journal-title":"Hypertension"},{"key":"2021113011170459100_B81","article-title":"Novel ACE2 truncate for acute kidney injury","author":"Mina Shirazi","year":"2019","journal-title":"ASN Abstarct"},{"key":"2021113011170459100_B82","doi-asserted-by":"publisher","first-page":"e0213096","DOI":"10.1371\/journal.pone.0213096","article-title":"Circulating angiotensin peptides levels in acute respiratory distress syndrome correlate with clinical outcomes: a pilot study","volume":"14","author":"Reddy","year":"2019","journal-title":"PLoS ONE"},{"key":"2021113011170459100_B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.03.005","article-title":"Kidney disease is associated with in-hospital death of patients with COVID-19","author":"Cheng","year":"2020","journal-title":"Kidney Int."},{"key":"2021113011170459100_B84","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.kint.2020.05.006","article-title":"Acute kidney injury in patients hospitalized with COVID-19","volume":"98","author":"Hirsch","year":"2020","journal-title":"Kidney Int."},{"key":"2021113011170459100_B85","first-page":"2367","article-title":"Coagulation and innate immune responses: can we view them separately?","volume":"114","author":"Delvaeye","year":"2009","journal-title":"Blood, J. Am. Soc. Hematol."},{"key":"2021113011170459100_B86","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/S0002-9149(01)01509-0","article-title":"Angiotensin, fibrinolysis, and vascular homeostasis","volume":"87","author":"Vaughan","year":"2001","journal-title":"Am. J. Cardiol."},{"key":"2021113011170459100_B87","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020040426","article-title":"Clinicopathological Features and Outcomes of Acute Kidney Injury in Critically Ill COVID-19 with Prolonged Disease Course: A Retrospective Cohort","author":"Xia","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"2021113011170459100_B88","doi-asserted-by":"publisher","DOI":"10.34067\/KID.0002652020","article-title":"Acute kidney injury associated with coronavirus disease 2019 in Urban New Orleans","author":"Mohamed","year":"2020","journal-title":"Kidney360"},{"key":"2021113011170459100_B89","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2020.3596","article-title":"Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US","author":"Gupta","year":"2020","journal-title":"JAMA Intern. Med."},{"key":"2021113011170459100_B90","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020050699","article-title":"COVID-19\u2013Associated Kidney Injury: A Case Series of Kidney Biopsy Findings","author":"Sharma","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"2021113011170459100_B91","article-title":"COVAN is the new HIVAN: the re-emergence of collapsing glomerulopathy with COVID-19","author":"Velez","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"2021113011170459100_B92","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1681\/ASN.2020050558","article-title":"AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL 1 High-Risk Genotype","volume":"31","author":"Wu","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"2021113011170459100_B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.05.025","article-title":"Thrombotic microangiopathy in a patient with COVID-19","author":"Jhaveri","year":"2020","journal-title":"Kidney Int."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/134\/21\/2791\/896701\/cs-2020-0484c.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/134\/21\/2791\/896701\/cs-2020-0484c.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T12:15:04Z","timestamp":1638274504000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/134\/21\/2791\/226868\/ACE2-the-kidney-and-the-emergence-of-COVID-19-two"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11]]},"references-count":93,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2020,11,13]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20200484","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"type":"print","value":"0143-5221"},{"type":"electronic","value":"1470-8736"}],"subject":[],"published-other":{"date-parts":[[2020,11]]},"published":{"date-parts":[[2020,11]]}}}