{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T23:46:45Z","timestamp":1779925605820,"version":"3.53.1"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Office of Rare Diseases Research"},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes, Digestive, and Kidney Diseases","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007270","name":"University of Michigan","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007270","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NephCure Kidney International"},{"name":"Halpin Foundation"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of experimental kidney disease. ACE2 is on the X chromosome, and in mice, deletion of ACE2 leads to the development of focal segmental glomerulosclerosis (FSGS). The relationship between sex and renal ACE2 expression in humans with kidney disease is a gap in current knowledge.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We studied renal tubulointerstitial microarray data and clinical variables from subjects with FSGS enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) study. We compared relationships between ACE2 expression and age, estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), interstitial fibrosis, tubular atrophy, and genes implicated in inflammation and fibrosis in male and female subjects.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>ACE2 mRNA expression was lower in the tubulointerstitium of males compared to females (<jats:italic>P<\/jats:italic> = 0.0026). Multiple linear regression analysis showed that ACE2 expression was related to sex and eGFR but not to age or treatment with renin angiotensin system blockade. ACE2 expression is also related to interstitial fibrosis, and tubular atrophy, in males but not in females. Genes involved in inflammation (<jats:italic>CCL2<\/jats:italic> and <jats:italic>TNF<\/jats:italic>) correlated with ACE2 expression in males (<jats:italic>TNF<\/jats:italic>: <jats:italic>r<\/jats:italic> = -0.65, <jats:italic>P<\/jats:italic> &lt; 0.0001; <jats:italic>CCL2<\/jats:italic>: <jats:italic>r<\/jats:italic> = -0.60, <jats:italic>P<\/jats:italic> &lt; 0.0001) but not in females. TGFB1, a gene implicated in fibrosis correlated with ACE2 in both sexes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Sex is an important determinant of ACE2 expression in the tubulointerstitium of the kidney in FSGS. Sex also influences the relationships between ACE2, kidney fibrosis, and expression of genes involved in kidney inflammation.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0252758","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T17:29:08Z","timestamp":1623086948000},"page":"e0252758","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6925-9753","authenticated-orcid":true,"given":"Nicholas A.","family":"Maksimowski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Scholey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4626-8320","authenticated-orcid":true,"given":"Vanessa R.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Nephrotic Syndrome Study Network (NEPTUNE)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"pone.0252758.ref001","doi-asserted-by":"crossref","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":"I Hamming","year":"2004","journal-title":"J Pathol"},{"key":"pone.0252758.ref002","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1002\/path.1670","article-title":"Renal ACE2 expression in human kidney disease","volume":"204","author":"A Lely","year":"2004","journal-title":"J Pathol"},{"key":"pone.0252758.ref003","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1681\/ASN.2020030276","article-title":"Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia","volume":"31","author":"G Pei","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"pone.0252758.ref004","doi-asserted-by":"crossref","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":"JS Hirsch","year":"2020","journal-title":"Kidney Int"},{"key":"pone.0252758.ref005","doi-asserted-by":"crossref","first-page":"14838","DOI":"10.1074\/jbc.M200581200","article-title":"Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase","volume":"277","author":"C Vickers","year":"2002","journal-title":"J Biol Chem"},{"key":"pone.0252758.ref006","doi-asserted-by":"crossref","DOI":"10.1161\/01.RES.87.5.e1","article-title":"A Novel Angiotensin-Converting Enzyme\u2013Related Carboxypeptidase (ACE2) Converts Angiotensin I to Angiotensin 1\u20139","volume":"87","author":"M Donoghue","year":"2000","journal-title":"Circ Res"},{"key":"pone.0252758.ref007","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.2353\/ajpath.2006.051091","article-title":"Loss of Angiotensin-Converting Enzyme-2 Leads to the Late Development of Angiotensin II-Dependent Glomerulosclerosis","volume":"168","author":"GY Oudit","year":"2006","journal-title":"Am J Pathol"},{"key":"pone.0252758.ref008","doi-asserted-by":"crossref","first-page":"438","DOI":"10.2353\/ajpath.2007.060977","article-title":"Loss of Angiotensin-Converting Enzyme-2 (Ace2) Accelerates Diabetic Kidney Injury","volume":"171","author":"DW Wong","year":"2007","journal-title":"Am J Pathol"},{"key":"pone.0252758.ref009","doi-asserted-by":"crossref","first-page":"529","DOI":"10.2337\/db09-1218","article-title":"Human recombinant ACE2 reduces the progression of diabetic nephropathy","volume":"59","author":"GY Oudit","year":"2010","journal-title":"Diabetes"},{"key":"pone.0252758.ref010","doi-asserted-by":"crossref","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":"EH Bae","year":"2017","journal-title":"Kidney Int"},{"key":"pone.0252758.ref011","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1053\/j.ajkd.2020.09.002","article-title":"Outcomes Among Patients Hospitalized With COVID-19 and Acute Kidney Injury","volume":"77","author":"JH Ng","year":"2021","journal-title":"Am J Kidney Dis"},{"key":"pone.0252758.ref012","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1056\/NEJMc2011400","article-title":"Multiorgan and Renal Tropism of SARS-CoV-2","volume":"383","author":"VG Puelles","year":"2020","journal-title":"N Engl J Med"},{"key":"pone.0252758.ref013","doi-asserted-by":"crossref","first-page":"e9610","DOI":"10.15252\/msb.20209610","article-title":"The protein expression profile of ACE2 in human tissues","volume":"16","author":"F Hikmet","year":"2020","journal-title":"Mol Syst Biol"},{"key":"pone.0252758.ref014","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1159\/000324521","article-title":"Expression of ACE and ACE2 in patients with hypertensive nephrosclerosis","volume":"34","author":"G Wang","year":"2011","journal-title":"Kidney Blood Press Res"},{"key":"pone.0252758.ref015","doi-asserted-by":"crossref","first-page":"c57","DOI":"10.1159\/000319648","article-title":"Increased ACE and decreased ACE2 expression in kidneys from patients with IgA nephropathy","volume":"117","author":"S Mizuiri","year":"2011","journal-title":"Nephron Clin Pract"},{"key":"pone.0252758.ref016","doi-asserted-by":"crossref","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":"HN Reich","year":"2008","journal-title":"Kidney Int"},{"key":"pone.0252758.ref017","doi-asserted-by":"crossref","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":"S Mizuiri","year":"2008","journal-title":"Am J Kidney Dis"},{"key":"pone.0252758.ref018","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13293-020-00301-y","article-title":"The impact of sex and gender on immunotherapy outcomes","volume":"11","author":"SL Klein","year":"2020","journal-title":"Biol Sex Differ"},{"key":"pone.0252758.ref019","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/nrneph.2017.181","article-title":"Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease","volume":"14","author":"JJ Carrero","year":"2018","journal-title":"Nat Rev Nephrol"},{"key":"pone.0252758.ref020","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12916-015-0275-x","article-title":"New anthropometry-based age- and sex-specific reference values for urinary 24-hour creatinine excretion based on the adult Swiss population","volume":"13","author":"V Forni Ogna","year":"2015","journal-title":"BMC Med"},{"key":"pone.0252758.ref021","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1093\/ndt\/gfm919","article-title":"The impact of sex in primary glomerulonephritis","volume":"23","author":"DC Cattran","year":"2008","journal-title":"Nephrol Dial Transplant"},{"key":"pone.0252758.ref022","first-page":"115","article-title":"Long-term prognosis of focal sclerosing glomerulonephritis. An analysis of 250 cases with particular regard to tubulointerstitial changes","volume":"33","author":"M Wehrmann","year":"1990","journal-title":"Clin Nephrol"},{"key":"pone.0252758.ref023","doi-asserted-by":"crossref","first-page":"e0241534","DOI":"10.1371\/journal.pone.0241534","article-title":"Kidney ACE2 expression: Implications for chronic kidney disease","volume":"15","author":"N Maksimowski","year":"2020","journal-title":"PLoS One"},{"key":"pone.0252758.ref024","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.2215\/CJN.08370812","article-title":"Digital Pathology Evaluation in the Multicenter Nephrotic Syndrome Study Network (NEPTUNE)","volume":"8","author":"L Barisoni","year":"2013","journal-title":"Clin J Am Soc Nephrol"},{"key":"pone.0252758.ref025","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1681\/ASN.2013121274","article-title":"MicroRNA-21 in glomerular injury","volume":"26","author":"JY Lai","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"pone.0252758.ref026","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.2337\/db06-0477","article-title":"Modular activation of nuclear factor-kappaB transcriptional programs in human diabetic nephropathy","volume":"55","author":"H Schmid","year":"2006","journal-title":"Diabetes"},{"key":"pone.0252758.ref027","article-title":"Characterization of the intrarenal renin-angiotensin system in experimental Alport syndrome","volume":"185","author":"EH Bae","year":"2015","journal-title":"Am J Pathol"},{"key":"pone.0252758.ref028","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.kint.2020.04.009","article-title":"Blockade of SARS-CoV-2 infection by recombinant soluble ACE2","volume":"97","author":"F Alhenc-Gelas","year":"2020","journal-title":"Kidney Int"},{"key":"pone.0252758.ref029","doi-asserted-by":"crossref","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","volume":"126","author":"M Gheblawi","year":"2020","journal-title":"Circ Res"},{"key":"pone.0252758.ref030","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/1042517021000021608","article-title":"Molecular Cloning, mRNA Expression and Chromosomal Localization of Mouse Angiotensin-converting Enzyme-related Carboxypeptidase (mACE2)","volume":"13","author":"T Komatsu","year":"2002","journal-title":"DNA Seq"},{"key":"pone.0252758.ref031","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1093\/ckj\/sfz092","article-title":"The longitudinal relationship between patient-reported outcomes and clinical characteristics among patients with focal segmental glomerulosclerosis in the Nephrotic Syndrome Study Network","volume":"13","author":"JP Troost","year":"2020","journal-title":"Clin Kidney J"},{"key":"pone.0252758.ref032","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1681\/ASN.2004070593","article-title":"Toronto Glomerulonephritis Registry Group. Focal and segmental glomerulosclerosis: definition and relevance of a partial remission","volume":"16","author":"S Troyanov","year":"2005","journal-title":"J Am Soc Nephrol"},{"key":"pone.0252758.ref033","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1681\/ASN.2005101095","article-title":"Gender Differences in the Renal Response to Renin-Angiotensin System Blockade","volume":"17","author":"JA Miller","year":"2006","journal-title":"J Am Soc Nephrol"},{"key":"pone.0252758.ref034","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1681\/ASN.2020040419","article-title":"Acute Kidney Injury in COVID-19: Emerging Evidence of a Distinct Pathophysiology","volume":"31","author":"D Batlle","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"pone.0252758.ref035","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/S0140-6736(16)32064-5","article-title":"Chronic Kidney Disease","volume":"389","author":"AC Webster","year":"2017","journal-title":"Lancet"},{"key":"pone.0252758.ref036","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s00467-015-3169-4","article-title":"Tubular atrophy in the pathogenesis of chronic kidney disease progression","volume":"31","author":"JR Schelling","year":"2016","journal-title":"Pediatr Nephrol"},{"key":"pone.0252758.ref037","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1289\/ehp.7337","article-title":"Urinary Creatinine Concentrations in the U.S. Population: Implications for Urinary Biologic Monitoring Measurements","volume":"113","author":"DB Barr","year":"2005","journal-title":"Environ Health Perspect"},{"key":"pone.0252758.ref038","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41420-020-0276-1","article-title":"ACE2 expression and sex disparity in COVID-19","volume":"6","author":"MC Gagliardi","year":"2020","journal-title":"Cell death Discov"},{"key":"pone.0252758.ref039","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/nature24265","article-title":"Landscape of X chromosome inactivation across human tissues","volume":"550","author":"T Tukiainen","year":"2017","journal-title":"Nature"},{"key":"pone.0252758.ref040","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/2042-6410-1-6","article-title":"Sex differences in renal angiotensin converting enzyme 2 (ACE2) activity are 17\u03b2-oestradiol-dependent and sex chromosome-independent","volume":"1","author":"J Liu","year":"2010","journal-title":"Biol Sex Differ"},{"key":"pone.0252758.ref041","doi-asserted-by":"crossref","first-page":"110287","DOI":"10.1016\/j.mehy.2020.110287","article-title":"Role of testosterone in COVID-19 patients\u2013A double-edged sword?","volume":"144","author":"AN Hussain","year":"2020","journal-title":"Med Hypotheses"},{"key":"pone.0252758.ref042","first-page":"E562","article-title":"Sex-derived attributes contributing to SARS-CoV-2 mortality","volume":"319","author":"N Chanana","year":"2020","journal-title":"Am J Physiol Metab"},{"key":"pone.0252758.ref043","doi-asserted-by":"crossref","first-page":"F1374","DOI":"10.1152\/ajprenal.00656.2011","article-title":"Differential regulation of circulating and renal ACE2 and ACE in hypertensive mRen2.Lewis rats with early-onset diabetes","volume":"302","author":"LM Yamaleyeva","year":"2012","journal-title":"Am J Physiol Renal Physiol"},{"key":"pone.0252758.ref044","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.phrs.2016.03.018","article-title":"ACE inhibition, ACE2 and angiotensin-(1-7) axis in kidney and cardiac inflammation and fibrosis","volume":"107","author":"AC Sim\u00f5es e Silva","year":"2016","journal-title":"Pharmacol Res"},{"key":"pone.0252758.ref045","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/bph.12159","article-title":"ACE2, angiotensin-(1\u20137) and Mas receptor axis in inflammation and fibrosis","volume":"169","author":"A Sim\u00f5es e Silva","year":"2013","journal-title":"Br J Pharmacol"},{"key":"pone.0252758.ref046","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1161\/HYPERTENSIONAHA.110.164244","article-title":"Prevention of angiotensin II-mediated renal oxidative stress, inflammation, and fibrosis by angiotensin-converting enzyme 2","volume":"57","author":"J Zhong","year":"2011","journal-title":"Hypertens (Dallas, Tex 1979)"},{"key":"pone.0252758.ref047","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.2169\/internalmedicine.4243-19","article-title":"Chronotherapy with a Renin-angiotensin System Inhibitor Ameliorates Renal Damage by Suppressing Intrarenal Renin-angiotensin System Activation","volume":"59","author":"T Aoki","year":"2020","journal-title":"Intern Med"},{"key":"pone.0252758.ref048","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0140-6736(98)10363-X","article-title":"Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria","volume":"354","author":"P Ruggenenti","year":"1999","journal-title":"Lancet (London, England)"},{"key":"pone.0252758.ref049","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1681\/ASN.2011121159","article-title":"Liver Angiotensinogen Is the Primary Source of Renal Angiotensin II","volume":"23","author":"T Matsusaka","year":"2012","journal-title":"J Am Soc Nephrol"},{"key":"pone.0252758.ref050","doi-asserted-by":"crossref","first-page":"H2373","DOI":"10.1152\/ajpheart.00426.2008","article-title":"Regulation of ACE2 in cardiac myocytes and fibroblasts","volume":"295","author":"PE Gallagher","year":"2008","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"pone.0252758.ref051","doi-asserted-by":"crossref","first-page":"1382","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","volume":"75","author":"AHJ Danser","year":"2020","journal-title":"Hypertens (Dallas, Tex 1979)"},{"key":"pone.0252758.ref052","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1159\/000513710","article-title":"Local Angiotensin-Converting Enzyme 2 Gene Expression in Kidney Allografts Is Not Affected by Renin-Angiotensin-Aldosterone Inhibitors","volume":"46","author":"M Cahova","year":"2021","journal-title":"Kidney Blood Press Res"},{"key":"pone.0252758.ref053","doi-asserted-by":"crossref","first-page":"1941","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","volume":"31","author":"J Wysocki","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"pone.0252758.ref054","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1113\/expphysiol.2007.041392","article-title":"Role of angiotensin-converting enzyme 2 and angiotensin(1\u20137) in 17\u03b2-oestradiol regulation of renal pathology in renal wrap hypertension in rats","volume":"93","author":"H Ji","year":"2008","journal-title":"Exp Physiol"},{"key":"pone.0252758.ref055","doi-asserted-by":"crossref","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":"J Lan","year":"2020","journal-title":"Nature"},{"key":"pone.0252758.ref056","doi-asserted-by":"crossref","first-page":"H296","DOI":"10.1152\/ajpheart.00755.2020","article-title":"Sex differences in COVID-19: candidate pathways, genetics of ACE2, and sex hormones","volume":"320","author":"A Viveiros","year":"2021","journal-title":"Am J Physiol Circ Physiol"},{"key":"pone.0252758.ref057","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/s41577-020-0378-2","article-title":"Sex differences in immune responses in COVID-19","volume":"20","author":"MD Park","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"pone.0252758.ref058","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1186\/s12882-020-02112-0","article-title":"The COVID-19 nephrology compendium: AKI, CKD, ESKD and transplantation","volume":"21","author":"S Kant","year":"2020","journal-title":"BMC Nephrol"},{"key":"pone.0252758.ref059","first-page":"24","article-title":"COVID-19 and Kidney Injury","volume":"103","author":"MR Lynch","year":"2020","journal-title":"R I Med J (2013)"},{"key":"pone.0252758.ref060","first-page":"e13814","article-title":"Acute kidney injury associated with COVID-19-Cumulative evidence and rationale supporting against direct kidney injury (infection)","author":"MS Parmar","year":"2020","journal-title":"Nephrology (Carlton)"},{"key":"pone.0252758.ref061","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1002\/path.5471","article-title":"Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19)","volume":"251","author":"AR Bourgonje","year":"2020","journal-title":"J Pathol"},{"key":"pone.0252758.ref062","doi-asserted-by":"crossref","first-page":"110024","DOI":"10.1016\/j.mehy.2020.110024","article-title":"COVID-19 as a viral functional ACE2 deficiency disorder with ACE2 related multi-organ disease","volume":"144","author":"R Gan","year":"2020","journal-title":"Med Hypotheses"},{"key":"pone.0252758.ref063","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.xkme.2020.03.006","article-title":"Estimated GFR Trajectories in Pediatric and Adult Nephrotic Syndrome: Results From the Nephrotic Syndrome Study Network (NEPTUNE)","volume":"2","author":"AR Smith","year":"2020","journal-title":"Kidney Med"},{"key":"pone.0252758.ref064","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1172\/JCI112521","article-title":"Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension","volume":"77","author":"R Zatz","year":"1986","journal-title":"J Clin Invest"},{"key":"pone.0252758.ref065","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1111\/pedi.13081","article-title":"An evaluation of renin-angiotensin system markers in youth with type 2 diabetes and associations with renal outcomes","volume":"21","author":"AB Dart","year":"2020","journal-title":"Pediatr Diabetes"},{"key":"pone.0252758.ref066","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1161\/HYPERTENSIONAHA.119.14071","article-title":"Ang II (Angiotensin II) Conversion to Angiotensin-(1\u20137) in the Circulation Is POP (Prolyloligopeptidase)-Dependent and ACE2 (Angiotensin-Converting Enzyme 2)-Independent","volume":"75","author":"P Serfozo","year":"2020","journal-title":"Hypertens (Dallas, Tex 1979)"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0252758","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T17:30:07Z","timestamp":1623087007000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0252758"}},"subtitle":[],"editor":[{"given":"Jaap A.","family":"Joles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,6,7]]},"references-count":66,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0252758","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,7]]}}}