{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:42:59Z","timestamp":1782276179426,"version":"3.54.5"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Adrenal venous sampling (AVS) is recognized as the gold standard for subtyping primary aldosteronism (PA), but its invasive nature and technical challenges limit its availability. A recent study reported that sodium chloride cotransporter (NCC) in urinary extracellular vesicles (uEVs) is a promising marker for assessing the biological activity of aldosterone and can be treated as a potential biomarker of PA. The current study was conducted to verify the hypothesis that the expression of NCC and its phosphorylated form (pNCC) in uEVs are different in various subtypes and genotypes of PA and can be used to select AVS candidates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 50 patients with PA were enrolled in the study. Urinary extracellular vesicles (uEVs) were isolated from spot urine samples using ultracentrifugation. NCC and pNCC expressions were tested in patients diagnosed with PA who underwent AVS. Sanger sequencing of <jats:italic>KCNJ5<\/jats:italic> was performed on DNA extracted from adrenal adenoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>pNCC (1.89 folds, <jats:italic>P<\/jats:italic>&amp;lt;.0001) and NCC (1.82 folds, <jats:italic>P<\/jats:italic>=0.0002) was more abundant in the uEVs in the high lateralization index (h-LI, \u2265 4) group than in the low LI (l-LI, &amp;lt; 4) group. Carriers of the somatic <jats:italic>KCNJ5<\/jats:italic> mutations, compared with non-carriers, had more abundant pNCC expression (2.16 folds, P=0.0039). Positive correlation between pNCC abundance and plasma aldosterone level was found in this study (R = 0.1220, <jats:italic>P<\/jats:italic> = 0.0129).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The expression of pNCC in uEVs in patients with PA with various subtypes and genotypes was different. It can be used as biomarker of AVS for PA subtyping.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.834409","type":"journal-article","created":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T06:27:31Z","timestamp":1649053651000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["The Role of Urinary Extracellular Vesicles Sodium Chloride Cotransporter in Subtyping Primary Aldosteronism"],"prefix":"10.3389","volume":"13","author":[{"given":"Linghui","family":"Kong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-jin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-guang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weili","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-020-0382-4","article-title":"Pathogenesis and Treatment of Primary Aldosteronism","volume":"16","author":"Zennaro","year":"2020","journal-title":"Nat Rev Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.09.057","article-title":"Primary Aldosteronism: JACC State-Of-the-Art Review","volume":"74","author":"Rossi","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30135-3","article-title":"Outcomes After Adrenalectomy for Unilateral Primary Aldosteronism: An International Consensus on Outcome Measures and Analysis of Remission Rates in an International Cohort","volume":"5","author":"Williams","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198785","article-title":"K+ Channel Mutations in Adrenal Aldosterone-Producing Adenomas and Hereditary Hypertension","volume":"331","author":"Choi","year":"2011","journal-title":"Science"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.eprac.2021.01.007","article-title":"KCNJ5 Mutation Contributes to Complete Clinical Success in Aldosterone-Producing Adenoma: A Study From a Single Center","volume":"27","author":"Zhang","year":"2021","journal-title":"Endocr Pract"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2019-00531","article-title":"KCNJ5 Somatic Mutation Is a Predictor of Hypertension Remission After Adrenalectomy for Unilateral Primary Aldosteronism","volume":"104","author":"Vilela","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000001578","article-title":"KCNJ5 Mutation as a Predictor for Resolution of Hypertension After Surgical Treatment of Aldosterone-Producing Adenoma","volume":"36","author":"Kitamoto","year":"2018","journal-title":"J Hypertens"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e3628\u201337","DOI":"10.1210\/clinem\/dgaa482","article-title":"The Concordance Between Imaging and Adrenal Vein Sampling Varies With Aldosterone-Driver Somatic Mutation","volume":"105","author":"Wannachalee","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(16)30100-0","article-title":"Adrenal Vein Sampling Versus CT Scan to Determine Treatment in Primary Aldosteronism: An Outcome-Based Randomised Diagnostic Trial","volume":"4","author":"Dekkers","year":"2016","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-4061","article-title":"The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline","volume":"101","author":"Funder","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-013-1407-9","article-title":"The Sodium Chloride Cotransporter SLC12A3: New Roles in Sodium, Potassium, and Blood Pressure Regulation","volume":"466","author":"Moes","year":"2014","journal-title":"Pflugers Arch"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00044.2018","article-title":"Regulation of the Renal NaCl Cotransporter and Its Role in Potassium Homeostasis","volume":"100","author":"Hoorn","year":"2020","journal-title":"Physiol Rev"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.148","article-title":"Isolation and Characterization of Urinary Extracellular Vesicles: Implications for Biomarker Discovery","volume":"13","author":"Merchant","year":"2017","journal-title":"Nat Rev Nephrol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e12093","DOI":"10.1002\/jev2.12093","article-title":"Urinary Extracellular Vesicles: A Position Paper by the Urine Task Force of the International Society for Extracellular Vesicles","volume":"10","author":"Erdbrugger","year":"2021","journal-title":"J Extracell Vesicles"},{"key":"B15","doi-asserted-by":"publisher","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The Biology, Function, and Biomedical Applications of Exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.198135","article-title":"The Phosphorylated Sodium Chloride Cotransporter in Urinary Exosomes is Superior to Prostasin as a Marker for Aldosteronism","volume":"60","author":"van der Lubbe","year":"2012","journal-title":"Hypertension"},{"key":"B17","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1681\/ASN.2015111221","article-title":"In Primary Aldosteronism, Mineralocorticoids Influence Exosomal Sodium-Chloride Cotransporter Abundance","volume":"28","author":"Wolley","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00463.2015","article-title":"An Immunoassay for Urinary Extracellular Vesicles","volume":"310","author":"Salih","year":"2016","journal-title":"Am J Physiol Renal Physiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000273","article-title":"Collection, Storage, Preservation, and Normalization of Human Urinary Exosomes for Biomarker Discovery","volume":"69","author":"Zhou","year":"2006","journal-title":"Kidney Int"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.03346","article-title":"Clinical Characteristics of Somatic Mutations in Chinese Patients With Aldosterone-Producing Adenoma","volume":"65","author":"Zheng","year":"2015","journal-title":"Hypertension"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100915","article-title":"High Dietary Potassium Causes Ubiquitin-Dependent Degradation of the Kidney Sodium-Chloride Cotransporter","volume":"297","author":"Kortenoeven","year":"2021","journal-title":"J Biol Chem"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00232.2019","article-title":"WNK Bodies Cluster WNK4 and SPAK\/OSR1 to Promote NCC Activation in Hypokalemia","volume":"318","author":"Thomson","year":"2020","journal-title":"Am J Physiol Renal Physiol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/ans.12470","article-title":"Mutations in KCNJ5 Determines Presentation and Likelihood of Cure in Primary Hyperaldosteronism","volume":"85","author":"Ip","year":"2015","journal-title":"ANZ J Surg"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.834409\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T06:27:33Z","timestamp":1649053653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.834409\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,4]]},"references-count":23,"alternative-id":["10.3389\/fendo.2022.834409"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.834409","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,4]]},"article-number":"834409"}}