{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:31:38Z","timestamp":1786480298277,"version":"build-2736575974"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","funder":[{"DOI":"10.13039\/100015539","name":"Commonwealth Government of Australia","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015539","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"crossref","award":["Potassium in Hypertension"],"award-info":[{"award-number":["Potassium in Hypertension"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Danish Independent Research Fund"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2022,5,26]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n Volume expansion induced a clear reduction in aquaporin 2 abundance in urinary extracellular vesicles.<\/jats:p>\n <\/jats:list-item>\n \n Changes in sodium-chloride cotransporter (NCC) and phosphorylated NCC may have been primarily due to diluted post-test urine samples and stable plasma potassium during the test.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Sodium chloride (NaCl) loading and volume expansion suppress the renin-angiotensin-aldosterone system to reduce renal tubular reabsorption of NaCl and water, but effects on the sodium-chloride cotransporter (NCC) and relevant renal transmembrane proteins that are responsible for this modulation in humans are less well investigated.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We used urinary extracellular vesicles (uEVs) as an indirect readout to assess renal transmembrane proteins involved in NaCl and water homeostasis in 44 patients with hypertension who had repeatedly raised aldosterone\/renin ratios undergoing infusion of 2 L of 0.9% saline over 4 hours.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n When measured by mass spectrometry in 13 patients, significant decreases were observed in NCC (median fold change [FC]=0.70); pendrin (FC=0.84); AQP2 (FC=0.62); and uEV markers, including ALIX (FC=0.65) and TSG101 (FC=0.66). Immunoblotting reproduced the reduction in NCC (FC=0.54), AQP2 (FC=0.42), ALIX (FC=0.52), and TSG101 (FC=0.55) in the remaining 31 patients, and demonstrated a significant decrease in phosphorylated NCC (pNCC; FC=0.49). However, after correction for ALIX, the reductions in NCC (FC=0.90) and pNCC (FC=1.00) were no longer apparent, whereas the significant decrease in AQP2 persisted (FC=0.62).<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n We conclude that (\n 1<\/jats:italic>\n ) decreases in NCC and pNCC, induced by acute NaCl loading and volume expansion, may be due to diluted post-test urines; (\n 2<\/jats:italic>\n ) the lack of change of NCC and pNCC when corrected for ALIX, despite a fall in plasma aldosterone, may be due to the lack of change in plasma K\n +<\/jats:sup>\n ; and (\n 3<\/jats:italic>\n ) the decrease in AQP2 may be due to a decrease in vasopressin in response to volume expansion.\n <\/jats:p>\n 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University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, Australia"},{"name":"Department of Nephrology, Royal Brisbane and Women\u2019s Hospital, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6249-4091","authenticated-orcid":false,"given":"Qi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Cowley","sequence":"additional","affiliation":[{"name":"Endocrine Hypertension Research Centre, University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, 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