{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:11:36Z","timestamp":1792883496691,"version":"4.5.0"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:bold>and objectives<\/jats:bold>\n                      The Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 study demonstrated a significant beneficial effect of the vasopressin V2 receptor antagonist tolvaptan on rates of kidney growth and eGFR decline in autosomal dominant polycystic kidney disease (ADPKD). This\n                      <jats:italic toggle=\"yes\">post hoc<\/jats:italic>\n                      analysis was performed to reassess the primary and secondary efficacy endpoints by CKD stage at baseline.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>In a phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, 1445 patients with ADPKD (age 18\u201350 years), with total kidney volume (TKV) \u2265750 ml and estimated creatinine clearance \u226560 ml\/min, were randomly assigned 2:1 to split-dose tolvaptan (45\/15, 60\/30, or 90\/30 mg daily as tolerated) or placebo. The primary endpoint was annualized rate of TKV change. Secondary endpoints included a composite endpoint of time to multiple composite ADPKD-related events (worsening kidney function, kidney pain, hypertension, and albuminuria) and rate of kidney function decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Tolvaptan reduced annualized TKV growth by 1.99%, 3.12%, and 2.61% per year (all\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001; subgroup\u2013treatment interaction,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.17) and eGFR decline by 0.40 in CKD1 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.23), 1.13 in CKD2 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001) and 1.66 ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      per year in CKD3 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001) with a trend for a positive subgroup-treatment interaction (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.07) across CKD1, CKD2 and CKD3. ADPKD-related events were less frequent in tolvaptan recipients than in placebo recipients among those with CKD1 (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.70\u20130.98;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.03) and those with CKD 3 (HR, 0.71; 95% CI, 0.57\u20130.89;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.003), but not among those with CKD2 (HR, 1.02; 95% CI, 0.85\u20131.21;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.86). Aquaresis-related adverse events (more frequent in the tolvaptan group) and ADPKD-related adverse events (more frequent in the placebo group) were not associated with CKD stage. Hypernatremia events in tolvaptan-treated patients with CKD3 and plasma aminotransferase elevations in tolvaptan-treated patients across CKD stages 1\u20133 occurred more frequently than in placebo recipients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This\n                      <jats:italic toggle=\"yes\">post hoc<\/jats:italic>\n                      analysis suggests clinically similar beneficial effects of tolvaptan in ADPKD across CKD stages 1\u20133.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.06300615","type":"journal-article","created":{"date-parts":[[2016,2,23]],"date-time":"2016-02-23T23:09:16Z","timestamp":1456268956000},"page":"803-811","source":"Crossref","is-referenced-by-count":142,"title":["Effect of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease by CKD Stage: Results from the TEMPO 3:4 Trial"],"prefix":"10.2215","volume":"11","author":[{"given":"Vicente E.","family":"Torres","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Higashihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Devuyst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlene B.","family":"Chapman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald T.","family":"Gansevoort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared J.","family":"Grantham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald D.","family":"Perrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime D.","family":"Blais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank S.","family":"Czerwiec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the TEMPO 3:4 Trial Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,2,23]]},"reference":[{"key":"B1-20230813","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/S0140-6736(07)60601-1","article-title":"Autosomal dominant polycystic kidney disease.","volume":"369","author":"Torres","year":"2007","journal-title":"Lancet"},{"key":"B2-20230813","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1056\/NEJMcp0804458","article-title":"Clinical practice. 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