{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:04:13Z","timestamp":1791313453211,"version":"4.3.1"},"reference-count":68,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,4,7]],"date-time":"2014-04-07T00:00:00Z","timestamp":1396828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:p>Autosomal dominant polycystic kidney disease (<jats:styled-content style=\"fixed-case\">ADPKD<\/jats:styled-content>) is characterized by bilateral renal cysts, kidney pain, hypertension, and progressive loss of renal function. It is a leading cause of end\u2010stage renal disease and the most common inherited kidney disease in the United States. Despite its prevalence, disease\u2010modifying treatment options do not currently exist. Tolvaptan is an orally active, selective arginine vasopressin V<jats:sub>2<\/jats:sub> receptor antagonist already in use for hyponatremia. Tolvaptan exhibits dose\u2010proportional pharmacokinetics with a half\u2010life of ~12\u00a0hours. Metabolism occurs through the cytochrome P450 3A4 isoenzyme, and tolvaptan is a substrate for P\u2010glycoprotein, resulting in numerous drug interactions. Recent research has highlighted the beneficial effect of tolvaptan on delaying the progression of <jats:styled-content style=\"fixed-case\">ADPKD<\/jats:styled-content>, which is the focus of this review. Pharmacologic, preclinical, and phase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> clinical trial studies have demonstrated that tolvaptan is an effective treatment option that targets underlying pathogenic mechanisms of <jats:styled-content style=\"fixed-case\">ADPKD<\/jats:styled-content>. Tolvaptan delays the increase in total kidney volume (surrogate marker for disease progression), slows the decline in renal function, and reduces kidney pain. However, tolvaptan has significant adverse effects including aquaretic effects (polyuria, nocturia, polydipsia) and elevation of aminotransferase enzyme concentrations with the potential for acute liver failure. Appropriate patient selection is critical to optimize long\u2010term benefits while minimizing adverse effects and hepatotoxic risk factors. Overall, tolvaptan is the first pharmacotherapeutic intervention to demonstrate significant benefit in the treatment of <jats:styled-content style=\"fixed-case\">ADPKD<\/jats:styled-content>, but practitioners and regulatory agencies must carefully weigh the risks versus benefits. Additional research should focus on incidence and risk factors of liver injury, cost\u2010effectiveness, clinical management of drug\u2013drug interactions, and long\u2010term disease outcomes.<\/jats:p>","DOI":"10.1002\/phar.1421","type":"journal-article","created":{"date-parts":[[2014,4,7]],"date-time":"2014-04-07T03:20:49Z","timestamp":1396840849000},"page":"605-616","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Review of Tolvaptan for Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1002","volume":"34","author":[{"given":"Brian P.","family":"Baur","sequence":"first","affiliation":[{"name":"University at Buffalo School of Pharmacy and Pharmaceutical Sciences Buffalo New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin J.","family":"Meaney","sequence":"additional","affiliation":[{"name":"University at Buffalo School of Pharmacy and Pharmaceutical Sciences Buffalo New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp0804458"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60601-1"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2009.128"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.76a.gr001"},{"key":"e_1_2_12_6_1","volume-title":"USRDS 2012 Annual data report: atlas of chronic kidney disease and end\u2010stage renal disease in the United States","author":"U.S. Renal Data System","year":"2012"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe1211857"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2008.03.003"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000334166"},{"key":"e_1_2_12_10_1","unstructured":"Otsuka Pharmaceutical Co. 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