{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:25:47Z","timestamp":1791771947708,"version":"4.3.4"},"reference-count":68,"publisher":"American Society for Clinical Investigation","issue":"14","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019120","name":"Otsuka America","doi-asserted-by":"crossref","award":["OAK-ISS-2021-001441"],"award-info":[{"award-number":["OAK-ISS-2021-001441"]}],"id":[{"id":"10.13039\/100019120","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["DK142878"],"award-info":[{"award-number":["DK142878"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["DK144863"],"award-info":[{"award-number":["DK144863"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["DK137307"],"award-info":[{"award-number":["DK137307"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:p>\n                    Renal water reabsorption is classically regulated by vasopressin V2 receptor (V2R) signaling through cyclic AMP and protein kinase A, driving apical accumulation of aquaporin-2 (AQP2). However, collecting duct water handling is also modulated by vasopressin-independent mechanisms. Here, we examined intracellular soluble urate as a vasopressin-independent regulator of AQP2 trafficking. Intracellular urate accumulation in collecting duct cells was mediated by enhanced apical urate uptake via GLUT9b and reduced apical urate efflux through ABCG2, triggering phosphodiesterase-4 activation, reduced cAMP, and downstream AMP-activated protein kinase (AMPK) activation. The resulting AQP2 accumulation at the apical membrane was independent of V2R signaling, required ongoing endocytosis, and was associated with features of postendocytic apical trafficking of internalized AQP2. In vivo ABCG2 inhibition with probenecid increased apical AQP2 abundance and markedly attenuated tolvaptan-induced polyuria in both wild-type and\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>RC\/RC<\/jats:sup>\n                    autosomal dominant polycystic kidney disease (ADPKD) mice in a uricase-independent manner while preserving tolvaptan\u2019s ADPKD-modifying efficacy. In a phase II trial with tolvaptan-treated patients with ADPKD, probenecid reduced urine volume and nocturia frequency. Together, these findings support a vasopressin-independent urate\/AMPK\/AQP2 pathway that regulates renal water handling and, in a preclinical ADPKD model, can uncouple cyst growth attenuation from the dose-limiting aquaretic effects of V2R antagonism.\n                  <\/jats:p>","DOI":"10.1172\/jci197021","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:01:15Z","timestamp":1781582475000},"source":"Crossref","is-referenced-by-count":1,"title":["GLUT9b- and ABCG2-mediated collecting duct urate transport uncovers a vasopressin-independent mechanism of renal water reabsorption"],"prefix":"10.1172","volume":"136","author":[{"given":"Mohamad","family":"Hadla","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Jacksonville, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Marc","family":"Mardirossian","sequence":"additional","affiliation":[{"name":"Division of 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