Pulmonary Embolism in a Patient With ADPKD Treated With Tolvaptan: From the Clinical Experience to the Analysis of the Food and Drug Administration Adverse Event Reporting System Registry

utosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder (estimated prevalence of 1 per 1000–1 per 2500 live births)1 characterized by the development and growth of multiple bilateral cysts eventually leading to end-stage renal disease and renal replacement therapy.1 Tolvaptan, a selective vasopressin V2 receptor antagonist, is currently the only pharmacologic agent approved for ADPKD capable of slowing the kidney cyst growth and the progression of kidney disease.2 The resulting aquaretic adverse events (AEs) (polyuria, pollakiuria, and nocturia) may cause dehydration and did not seem to diminish over time,2 thus supporting the need to inform patients for adequate liquid intake and maintaining long-term vigilance. Data on the risk/benefit profile of tolvaptan in ADPKD come mainly from randomized controlled trials and small real-world studies.3 The latest prospective, multinational, open-label safety study enrolling subjects who completed previous trials (median exposure 651 days) confirmed the occurrence of treatmentemergent aquaretic AEs and the importance of tight hepatic monitoring as effective risk minimization strategy.4 Therefore, postmarketing studies are needed to evaluate rare and unexpected AEs, which are not fully appreciated in randomized controlled trials.5 We herein describe the occurrence of acute pulmonary thromboembolism in a patient with risk factors exposed to tolvaptan. To evaluate the possible association between tolvaptan and thromboembolism, we also analyzed the Food and Drug Administration Adverse Event Reporting System