{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:48:08Z","timestamp":1792723688043,"version":"4.5.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:p>The vasopressin\u2013cAMP\u2013osmolality axis is abnormal in autosomal dominant polycystic kidney disease (ADPKD). In the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 Trial, a 3-year randomized, placebo-controlled trial in adults, the vasopressin V2 receptor antagonist tolvaptan slowed ADPKD progression in patients with preserved GFR. Here, we investigated the determinants of baseline urine osmolality (Uosm) and its value as a severity marker of ADPKD, the factors influencing the response to tolvaptan, and whether change in Uosm associated with key trial end points. At baseline, lower Uosm independently associated with female sex, presence of hypertension, lower eGFR, higher total kidney volume (TKV), and higher age. Tolvaptan consistently reduced Uosm by 200\u2013300 mOsm\/kg over 36 months. The Uosm response to tolvaptan depended on baseline eGFR and Uosm. Subjects with greater change in Uosm experienced a significant reduction in clinical progression events. Among subjects receiving tolvaptan, those with a greater suppression of Uosm had slower renal function decline. Assessment at follow-up, off medication, revealed a significant decrease in Uosm in both placebo and treated groups. Tolvaptan significantly increased plasma osmolality, which returned to baseline at follow-up. In conclusion, baseline Uosm in ADPKD reflects age, renal function, and TKV, and baseline Uosm, eGFR, and TKV influence the effect of tolvaptan on Uosm. The greatest renal benefit occurred in subjects achieving greater suppression of Uosm, that is, those with better eGFR at baseline. These results support the link between vasopressin V2 receptor signaling and ADPKD progression.<\/jats:p>","DOI":"10.1681\/asn.2016040448","type":"journal-article","created":{"date-parts":[[2016,12,5]],"date-time":"2016-12-05T22:00:30Z","timestamp":1480975230000},"page":"1592-1602","source":"Crossref","is-referenced-by-count":93,"title":["Urine Osmolality, Response to Tolvaptan, and Outcome in Autosomal Dominant Polycystic Kidney Disease: Results from the TEMPO 3:4 Trial"],"prefix":"10.1681","volume":"28","author":[{"given":"Olivier","family":"Devuyst","sequence":"first","affiliation":[{"name":"Institute of Physiology, University of Zurich, Zurich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlene B.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Chicago, Chicago, Illinois;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron T.","family":"Gansevoort","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Higashihara","sequence":"additional","affiliation":[{"name":"Department of Urology, Kyorin University School of Medicine, Mitaka, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald D.","family":"Perrone","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente E.","family":"Torres","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime D.","family":"Blais","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank S.","family":"Czerwiec","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,12,5]]},"reference":[{"key":"B1-20230829","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1056\/NEJMcp0804458","article-title":"Clinical practice. 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