{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:06:00Z","timestamp":1790946360306,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["17CVD05"],"award-info":[{"award-number":["17CVD05"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Using urinary extracellular vesicles (uEVs), we have demonstrated the functional \u2018renal\u2010K switch\u2019 mechanism (the WNK\u2010SPAK\u2010NCC pathway) in both healthy subjects and those with primary aldosteronism. The close relationship between blood pressure and CKD has led to the hypothesis that high potassium intake may be reno\u2010protective through the same mechanism. This study used uEVs to evaluate whether plasma potassium negatively correlates with NCC and its phosphorylation (pNCC) in patients with CKD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Morning blood and second morning urine were collected on a single occasion between 8 and 11\u2009AM from patients with various CKD stages. Plasma potassium levels were assessed by a local pathology laboratory. uEVs were obtained by progressive ultracentrifugation, and NCC and pNCC were analysed by western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Correlation analyses among 23 patients with CKD revealed the abundance of NCC (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.46, <jats:italic>p<\/jats:italic>\u2009=\u20090.0003) and pNCC (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.30, <jats:italic>p<\/jats:italic>\u2009=\u20090.0067) strongly and negatively correlate with plasma potassium. The negative correlations persist among 18 patients who did not receive SGLT2 inhibitors or K\u2010binders (NCC: <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.5, <jats:italic>p<\/jats:italic>\u2009=\u20090.002; pNCC: <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.30, <jats:italic>p<\/jats:italic>\u2009=\u20090.03) and the negative trends remain among 5 patients who received either SGLT2 inhibitors or K\u2010binders (NCC: <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.64, <jats:italic>p<\/jats:italic>\u2009=\u20090.11; pNCC: <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.42, <jats:italic>p<\/jats:italic>\u2009=\u20090.24).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients with CKD, there are negative correlations between NCC and pNCC in uEVs and plasma potassium, which appear independent of eGFR. This suggests that the mechanism at play is distinct from the overall kidney function, and potassium supplement within a safe level may assist in natriuresis and improve cardiovascular outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nep.70017","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T12:01:47Z","timestamp":1741953707000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Plasma Potassium Negatively Correlates With Sodium Chloride Cotransporter Abundance and Phosphorylation in Urinary Extracellular Vesicles From Patients With Chronic Kidney Disease"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9610-0943","authenticated-orcid":false,"given":"Aihua","family":"Wu","sequence":"first","affiliation":[{"name":"Endocrine Hypertension Research Centre The University of Queensland Frazer Institute, Greenslopes and Princess Alexandra Hospitals  Brisbane Australia"},{"name":"Department of Medicine Vanderbilt University Medical Centre  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Wolley","sequence":"additional","affiliation":[{"name":"Endocrine Hypertension Research Centre The University of Queensland Frazer Institute, Greenslopes and Princess Alexandra Hospitals  Brisbane Australia"},{"name":"Department of Nephrology Royal Brisbane and Women's Hospital  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Vesey","sequence":"additional","affiliation":[{"name":"Translational Research Institute The University of Queensland Centre for Kidney Disease Research  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.","family":"Terker","sequence":"additional","affiliation":[{"name":"Department of Medicine Vanderbilt University Medical Centre  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Welling","sequence":"additional","affiliation":[{"name":"Department of Medicine and Physiology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"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 The University of Queensland Frazer Institute, Greenslopes and Princess Alexandra Hospitals  Brisbane 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