{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:24:25Z","timestamp":1791815065371,"version":"4.3.4"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>\n                    Distal tubular sodium retention is a potent driver of hypertension, and the thiazide\u2013sensitive sodium-chloride cotransporter (NCC) has a key role in this process. In humans, factors regulating NCC are unclear, but in animal models, aldosterone is a potent regulator, possibly\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    effects on plasma potassium. We studied the effects of the mineralocorticoid fludrocortisone on the abundance of NCC and its phosphorylated form (pNCC) as well as WNK lysine deficient protein kinase 4 (WNK4) and STE20\/SPS1\u2013related, proline alanine\u2013rich kinase (SPAK) in human urinary exosomes. We isolated exosomes from daily urine samples in 25 patients undergoing fludrocortisone suppression testing (100\n                    <jats:italic toggle=\"yes\">\u03bc<\/jats:italic>\n                    g every 6 hours for 4 days) to diagnose or exclude primary aldosteronism. Over the course of the test, NCC levels increased 3.68-fold (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt;0.01) and pNCC levels increased 2.73-fold (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt;0.01) relative to baseline. The ratio of pNCC\/NCC dropped by 48% (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt;0.01). The abundance of WNK4 increased 3.23-fold (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt;0.01), but SPAK abundance did not change significantly (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    =0.14). Plasma potassium concentration strongly and negatively correlated with pNCC, NCC, and WNK4 abundance (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt;0.001 for all). This study shows that, in humans, mineralocorticoid administration is associated with a rapid increase in abundance of NCC and pNCC, possibly\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    the WNK pathway. These effects may be driven by changes in plasma potassium.\n                  <\/jats:p>","DOI":"10.1681\/asn.2015111221","type":"journal-article","created":{"date-parts":[[2016,7,5]],"date-time":"2016-07-05T22:29:00Z","timestamp":1467757740000},"page":"56-63","source":"Crossref","is-referenced-by-count":63,"title":["In Primary Aldosteronism, Mineralocorticoids Influence Exosomal Sodium-Chloride Cotransporter Abundance"],"prefix":"10.1681","volume":"28","author":[{"given":"Martin J.","family":"Wolley","sequence":"first","affiliation":[{"name":"Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Brisbane, Australia;"},{"name":"Department of Nephrology, Royal Brisbane and Women\u2019s Hospital, Brisbane, Australia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Wu","sequence":"additional","affiliation":[{"name":"Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Brisbane, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengxin","family":"Xu","sequence":"additional","affiliation":[{"name":"Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Brisbane, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Brisbane, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Fenton","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Stowasser","sequence":"additional","affiliation":[{"name":"Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Brisbane, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,7,5]]},"reference":[{"key":"B1-20230819","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0092-8674(01)00241-0","article-title":"Molecular mechanisms of human hypertension.","volume":"104","author":"Lifton","year":"2001","journal-title":"Cell"},{"key":"B2-20230819","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1007\/s00467-014-2956-7","article-title":"Gordon Syndrome: A continuing story.","volume":"30","author":"O\u2019Shaughnessy","year":"2015","journal-title":"Pediatr 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