Real-World Tolvaptan Use in Autosomal Dominant Polycystic Kidney Disease

Key Points Twenty-seven percent of patients with autosomal dominant polycystic kidney disease discontinued tolvaptan in a real-world cohort in the midwestern United States. Most patients maintained tolvaptan on lower doses than trials, and a minority tolerated above the 45 mg ( am )/15 mg ( pm ) starting dosage. Adverse effects, specifically aquaretic side effects, strongly influenced tolvaptan tolerability, dosage titration, and discontinuation. Background Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disease leading to kidney failure. Tolvaptan, a vasopressin V2 receptor antagonist, is the only medication approved by the US Food and Drug Administration for slowing kidney growth in individuals with rapidly progressive ADPKD, but its long-term tolerability and effective implementation has yet to be studied, particularly in real-world clinical settings within the United States. Methods This retrospective cohort study examined adults with ADPKD treated with tolvaptan at the University of Kansas Medical Center and the University of Iowa Hospitals & Clinics from May 2018 to April 2023. Data on demographics, clinical characteristics, tolvaptan dosage, and treatment duration were collected from electronic health records for an average follow-up duration of 28.2 months (interquartile range: 8.5–47.1 months). The study focused on examining tolvaptan dosage trends, treatment discontinuation reasons, and the impact of aquaretic side effects on dosage and adherence. Results Of 134 patients, 27% stopped tolvaptan during the observational period, with 10.4% of the cohort withdrawing from treatment due to intolerance of aquaretic side effects. Most patients maintained a lower tolvaptan dosage (≤45/15 mg) than in clinical trials, with two thirds of individuals who underwent dosage adjustment undergoing net decrease in dosage. Adverse effects significantly influenced and dosage decisions, presenting a potential early barrier for adherence, particularly in female patients. Conclusions The study highlights real-world challenges in the use of tolvaptan for ADPKD, particularly for side effects leading to high discontinuation rates and dosage adjustments. These findings underscore the need for standardized and improved management strategies to enhance tolerability and adherence, offering insights for future research and practice in the treatment of ADPKD with tolvaptan.