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However, it is not clear whether TLV addition is effective for advanced CKD patients with heart failure.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>An open-label, parallel-group randomized trial was performed. The subjects were 33 patients with CKD stage G3\u2013G5 who had fluid overload despite taking 20\u2013100\u00a0mg\/day FUR. They were divided into two groups: a group administered 15\u00a0mg\/day TLV plus their original FUR dose for 7\u00a0days (TLV group), and a group administered 120\u2013200\u00a0mg\/day FUR (i.e., 100\u00a0mg\/day over their previous dose) for 7\u00a0days (FUR group).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The mean change in urine volume was significantly higher in the TLV group compared to the FUR group (637\u00a0ml vs 119\u00a0ml; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). The difference was greater when the urine osmolality before treatment was high. Serum creatinine was increased only in the FUR group. The incidence of worsening renal function (WRF) was significantly lower in the TLV group (18.8% vs 58.8%; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Serum sodium decreased significantly in the FUR group, but did not change in the TLV group.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In patients with advanced CKD with fluid overload, the addition of TLV achieved a significantly higher urine volume with less adverse effects on renal function compared with increasing the dose of FUR. The efficacy and safety of TLV were higher in patients who had higher urine osmolality and lower serum sodium before treatment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Clinical trial registration<\/jats:title>\n                <jats:p>UMIN000014763.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10157-022-02224-x","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T15:09:31Z","timestamp":1650985771000},"page":"851-858","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Efficacy of tolvaptan on advanced chronic kidney disease with heart failure: a randomized controlled trial"],"prefix":"10.1007","volume":"26","clinical-trial-number":[{"clinical-trial-number":"umin000014763","registry":"10.18810\/umin-japan"}],"author":[{"given":"Shiro","family":"Komiya","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari","family":"Katsumata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moe","family":"Ozawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Haze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rina","family":"Kawano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Ohki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shota","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanae","family":"Saka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kouichi","family":"Tamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5824-3652","authenticated-orcid":false,"given":"Nobuhito","family":"Hirawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,4,26]]},"reference":[{"issue":"931","key":"2224_CR1","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1136\/pmj.79.931.268","volume":"79","author":"LK De Bruyne","year":"2003","unstructured":"De Bruyne LK. 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