{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:28:34Z","timestamp":1793035714254,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2023,1]]},"abstract":"\n Background<\/jats:title>\n Tolvaptan slows expansion of kidney volume and kidney function decline in adults with autosomal dominant polycystic kidney disease (ADPKD). Progression during childhood could be treated before irreversible kidney damage occurs, but trial data are lacking. We evaluated the safety and efficacy of tolvaptan in children\/adolescents with ADPKD.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This was the 1-year, randomized, double-blind, portion of a phase 3b, two-part trial being conducted at 20 academic pediatric nephrology centers. Key eligibility criteria were ADPKD and eGFR \u226560 ml\/min per 1.73 m\n 2<\/jats:sup>\n . Participants aged 12\u201317 years were the target group (group 1, enrollment goal\n n<\/jats:italic>\n \u226560); participants aged 4\u201311 years could additionally enroll (group 2, anticipated enrollment approximately 40). Treatments were tolvaptan or placebo titrated by body weight and tolerability. Coprimary end points, change from baseline in spot urine osmolality and specific gravity at week 1, assessed inhibition of antidiuretic hormone activity. The key secondary end point was change in height-adjusted total kidney volume (htTKV) to month 12 in group 1. Additional end points were safety\/tolerability and quality of life. Statistical comparisons were exploratory and\n post hoc<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among the 91 randomized (group 1,\n n<\/jats:italic>\n =66; group 2,\n n<\/jats:italic>\n =25), least squares (LS) mean reduction (\u00b1SEM) in spot urine osmolality at week 1 was greater with tolvaptan (\u2212390 [28] mOsm\/kg) than placebo (\u221290 [29] mOsm\/kg;\n P<\/jats:italic>\n <0.001), as was LS mean reduction in specific gravity (\u22120.009 [0.001] versus \u22120.002 [0.001];\n P<\/jats:italic>\n <0.001). In group 1, the 12-month htTKV increase was 2.6% with tolvaptan and 5.8% with placebo (\n P<\/jats:italic>\n >0.05). For tolvaptan and placebo, respectively, 65% and 16% of subjects experienced aquaretic adverse events, and 2% and 0% experienced hypernatremia. There were no elevated transaminases or drug-induced liver injuries. Four participants discontinued tolvaptan, and three discontinued placebo. Quality-of-life assessments remained stable.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Tolvaptan exhibited pharmacodynamic activity in pediatric ADPKD. Aquaretic effects were manageable, with few discontinuations.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial registry name and registration number:<\/jats:title>\n Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease) NCT02964273.<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.0000000000000022","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T09:01:04Z","timestamp":1674205264000},"page":"36-46","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":44,"title":["Tolvaptan for Children and Adolescents with Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.2215","volume":"18","author":[{"given":"Djalila","family":"Mekahli","sequence":"first","affiliation":[{"name":"PKD Research Group, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium"},{"name":"Department of Pediatric Nephrology, University Hospital of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Guay-Woodford","sequence":"additional","affiliation":[{"name":"Center for Translational Research, Children's National Research Institute, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Cadnapaphornchai","sequence":"additional","affiliation":[{"name":"Rocky Mountain Pediatric Kidney Center, Rocky Mountain Hospital for Children at Presbyterian\/St. Luke's Medical Center, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry A.","family":"Greenbaum","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieczyslaw","family":"Litwin","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kidney Transplantation and Arterial Hypertension, Children's Memorial Health Institute, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Seeman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic"},{"name":"Department of Pediatrics, Dr. von Hauner Children's Hospital, LMU Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Dandurand","sequence":"additional","affiliation":[{"name":"Cerevel Therapeutics, Cambridge, Massachusetts"},{"name":"Otsuka Pharmaceutical Development & Commercialization, Princeton, New Jersey (former)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Shi","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development & Commercialization, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Sikes","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development & Commercialization, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Shoaf","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development & Commercialization, Princeton, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, University Children's Hospital Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"B1-20250823","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.ekir.2019.05.015","article-title":"ADPedKD Consortium. 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