{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:06:44Z","timestamp":1780315604645,"version":"3.54.1"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007132","name":"Otsuka Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007132","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Nephrol"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is a progressive condition that eventually leads to end-stage renal disease. A phase 3 trial of tolvaptan (TEMPO 3:4; NCT00428948) and its open-label extension (TEMPO Extension Japan: TEMPO-EXTJ; NCT01280721) were conducted in patients with ADPKD. In this post hoc analysis, effects on renal function and the safety profile of tolvaptan were assessed over a long-term period that included the 3-year TEMPO 3:4 and the approximately 3-year TEMPO-EXTJ trials.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Patients from Japanese trial sites who completed TEMPO 3:4 were offered participation in TEMPO-EXTJ. Patients whose efficacy parameters were measured at year 2 in TEMPO-EXTJ for efficacy evaluation were included. The annual slope of the estimated glomerular filtration rate (eGFR) and growth in total kidney volume (TKV) were analyzed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In patients who received tolvaptan in TEMPO 3:4 and TEMPO-EXTJ, the annual slope of eGFR (mL\/min\/1.73 m<jats:sup>2<\/jats:sup>) was \u2212\u00a03.480 in TEMPO 3:4 and \u2212\u00a03.417 in TEMPO-EXTJ, with no apparent effect of an approximately 3.6-month off-treatment interval between the two trials. In patients who received a placebo in TEMPO 3:4 before initiating tolvaptan in TEMPO-EXTJ, the slope of eGFR was significantly less steep from TEMPO 3:4 (\u2212\u00a04.287) to TEMPO-EXTJ (\u2212\u00a03.364), a difference of 0.923 (<jats:italic>P<\/jats:italic>\u2009=\u20090.0441).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The TEMPO-EXTJ trial supports a sustained beneficial effect of tolvaptan on eGFR. In patients who received a placebo in TEMPO 3:4, initiation of tolvaptan in TEMPO-EXTJ was associated with a significant slowing of eGFR decline.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10157-021-02083-y","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T16:03:02Z","timestamp":1622822582000},"page":"1003-1010","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effect of tolvaptan in Japanese patients with autosomal dominant polycystic kidney disease: a post hoc analysis of TEMPO 3:4 and TEMPO Extension Japan"],"prefix":"10.1007","volume":"25","author":[{"given":"Satoru","family":"Muto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Shibasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuki","family":"Ibuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Horie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"key":"2083_CR1","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1016\/S0140-6736(07)60601-1","volume":"369","author":"VE Torres","year":"2007","unstructured":"Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet. 2007;369:1287\u2013301.","journal-title":"Lancet"},{"key":"2083_CR2","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1056\/NEJMcp0804458","volume":"359","author":"JJ Grantham","year":"2008","unstructured":"Grantham JJ. Clinical practice. Autosomal dominant polycystic kidney disease. N Engl J Med. 2008;359:1477\u201385.","journal-title":"N Engl J Med"},{"key":"2083_CR3","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1007\/s00467-014-2882-8","volume":"30","author":"JJ Grantham","year":"2015","unstructured":"Grantham JJ. Rationale for early treatment of polycystic kidney disease. Pediatr Nephrol. 2015;30:1053\u201362.","journal-title":"Pediatr Nephrol"},{"key":"2083_CR4","doi-asserted-by":"publisher","first-page":"2407","DOI":"10.1056\/NEJMoa1205511","volume":"367","author":"VE Torres","year":"2012","unstructured":"Torres VE, Chapman AB, Devuyst O, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012;367:2407\u201318.","journal-title":"N Engl J Med"},{"key":"2083_CR5","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1007\/s10157-015-1086-2","volume":"19","author":"S Muto","year":"2015","unstructured":"Muto S, Kawano H, Higashihara E, et al. The effect of tolvaptan on autosomal dominant polycystic kidney disease patients: a subgroup analysis of the Japanese patient subset from TEMPO 3:4 trial. Clin Exp Nephrol. 2015;19:867\u201377.","journal-title":"Clin Exp Nephrol"},{"issue":"Suppl 1","key":"2083_CR6","doi-asserted-by":"publisher","first-page":"S33","DOI":"10.1007\/s10557-011-6304-x","volume":"25","author":"M Matsuzaki","year":"2011","unstructured":"Matsuzaki M, Hori M, Izumi T, for the Tolvaptan Investigators. Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled Study (QUEST Study). Cardiovasc Drugs Ther. 2011;25(Suppl 1):S33\u201345.","journal-title":"Cardiovasc Drugs Ther"},{"key":"2083_CR7","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1111\/hepr.12098","volume":"44","author":"I Sakaida","year":"2014","unstructured":"Sakaida I, Kawazoe S, Kajimura K, et al. Tolvaptan for improvement of hepatic edema: a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Hepatol Res. 2014;44:73\u201382.","journal-title":"Hepatol Res"},{"key":"2083_CR8","doi-asserted-by":"publisher","first-page":"93","DOI":"10.2147\/DHPS.S142825","volume":"9","author":"S Muto","year":"2017","unstructured":"Muto S, Okada T, Yasuda M, et al. Long-term safety profile of tolvaptan in autosomal dominant polycystic kidney disease patients: TEMPO Extension Japan trial. Drug Healthc Patient Saf. 2017;9:93\u2013104.","journal-title":"Drug Healthc Patient Saf"},{"key":"2083_CR9","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1053\/j.ajkd.2008.12.034","volume":"53","author":"S Matsuo","year":"2009","unstructured":"Matsuo S, Imai E, Horio M, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982\u201392.","journal-title":"Am J Kidney Dis"},{"key":"2083_CR10","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1093\/ndt\/gfx043","volume":"33","author":"VE Torres","year":"2018","unstructured":"Torres VE, Chapman AB, Devuyst O, et al. Multicenter, open-label, extension trial to evaluate the long-term efficacy and safety of early versus delayed treatment with tolvaptan in autosomal dominant polycystic kidney disease: the TEMPO 4:4 Trial. Nephrol Dial Transplant. 2018;33:477\u201389.","journal-title":"Nephrol Dial Transplant"},{"key":"2083_CR11","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1056\/NEJMoa1710030","volume":"377","author":"VE Torres","year":"2017","unstructured":"Torres VE, Chapman AB, Devuyst O, REPRISE Trial Investigators, et al. Tolvaptan in later-stage autosomal dominant polycystic kidney disease. N Engl J Med. 2017;377:1930\u201342.","journal-title":"N Engl J Med"}],"container-title":["Clinical and Experimental Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10157-021-02083-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10157-021-02083-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10157-021-02083-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T10:20:58Z","timestamp":1628677258000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10157-021-02083-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,4]]},"references-count":11,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["2083"],"URL":"https:\/\/doi.org\/10.1007\/s10157-021-02083-y","relation":{},"ISSN":["1342-1751","1437-7799"],"issn-type":[{"value":"1342-1751","type":"print"},{"value":"1437-7799","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,4]]},"assertion":[{"value":"25 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"SM and SH have received research funding, honoraria for presentations, paid travels, and consulting and advisory board fees from Otsuka Pharmaceutical Co., Ltd., Japan, and belong to an endowed department sponsored by Otsuka Pharmaceutical Co., Ltd., Japan. In addition, SH has been a medical advisor of the TEMPO-EXTJ trial. TO and YS are employees of Otsuka Pharmaceutical Co., Ltd., Japan, and TI is a former employee of Otsuka Pharmaceutical Co., Ltd., Japan.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"These trials were conducted in accordance with ethical principles originating from the Declaration of Helsinki and in compliance with good clinical practice guidelines. The protocols were approved by the institutional review board at each trial site. The first IRB approval was issued by Niigata University (IRB approval number: CH22-010). Written informed consent was obtained from all participating patients.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}