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Review of Tolvaptan for Autosomal Dominant Polycystic Kidney Disease
Author(s) -
Baur Brian P.,
Meaney Calvin J.
Publication year - 2014
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.1421
Subject(s) - tolvaptan , medicine , autosomal dominant polycystic kidney disease , polycystic kidney disease , renal function , kidney disease , adverse effect , hyponatremia , kidney , urology , intensive care medicine
Autosomal dominant polycystic kidney disease ( ADPKD ) is characterized by bilateral renal cysts, kidney pain, hypertension, and progressive loss of renal function. It is a leading cause of end‐stage renal disease and the most common inherited kidney disease in the United States. Despite its prevalence, disease‐modifying treatment options do not currently exist. Tolvaptan is an orally active, selective arginine vasopressin V 2 receptor antagonist already in use for hyponatremia. Tolvaptan exhibits dose‐proportional pharmacokinetics with a half‐life of ~12 hours. Metabolism occurs through the cytochrome P450 3A4 isoenzyme, and tolvaptan is a substrate for P‐glycoprotein, resulting in numerous drug interactions. Recent research has highlighted the beneficial effect of tolvaptan on delaying the progression of ADPKD , which is the focus of this review. Pharmacologic, preclinical, and phase II and III clinical trial studies have demonstrated that tolvaptan is an effective treatment option that targets underlying pathogenic mechanisms of ADPKD . 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‐term benefits while minimizing adverse effects and hepatotoxic risk factors. Overall, tolvaptan is the first pharmacotherapeutic intervention to demonstrate significant benefit in the treatment of ADPKD , 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‐effectiveness, clinical management of drug–drug interactions, and long‐term disease outcomes.

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