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However, some patients discontinue tolvaptan because of severe adverse aquaretic events. This open-label, randomized, controlled, counterbalanced, crossover trial investigated the effects of trichlormethiazide, a thiazide diuretic, in patients with ADPKD receiving tolvaptan (n\u2009=\u200910) who randomly received antihypertensive therapy with or without trichlormethiazide for 12\u00a0weeks. The primary and secondary outcomes included amount and osmolarity of 24-h urine and health-related quality-of-life (HRQOL) parameters assessed by the Kidney Disease Quality of Life-Short Form questionnaire, renal function slope, and plasma\/urinary biomarkers associated with disease progression. There was a significant reduction in urine volume (3348\u2009\u00b1\u2009584 vs. 4255\u2009\u00b1\u2009739\u00a0mL;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001) and a significant increase in urinary osmolarity (182.5\u2009\u00b1\u200938.1 vs. 141.5\u2009\u00b1\u200938.1\u00a0mOsm;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.001) in patients treated with trichlormethiazide. Moreover, trichlormethiazide improved the following HRQOL subscales: effects of kidney disease, sleep, emotional role functioning, social functioning, and role\/social component summary. No significant differences were noted in renal function slope or plasma\/urinary biomarkers between patients treated with and without trichlormethiazide. In patients with ADPKD treated with tolvaptan, trichlormethiazide may improve tolvaptan tolerability and HRQOL parameters.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-97113-w","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T08:22:07Z","timestamp":1630657327000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The effect of trichlormethiazide in autosomal dominant polycystic kidney disease patients receiving tolvaptan: a randomized crossover controlled trial"],"prefix":"10.1038","volume":"11","author":[{"given":"Kiyotaka","family":"Uchiyama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chigusa","family":"Kitayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akane","family":"Yanai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Ishibashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,3]]},"reference":[{"key":"97113_CR1","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/S0140-6736(18)32782-X","volume":"393","author":"E Cornec-Le Gall","year":"2019","unstructured":"Cornec-Le Gall, E., Alam, A. & Perrone, R. 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