Tolvaptan in ADPKD Beyond Trials: Tolerability, Monitoring, and Real-World Outcomes

Abstract Background Tolvaptan is the only approved disease-modifying therapy for autosomal dominant polycystic kidney disease (ADPKD). Real-world evidence on its safety and tolerability remains limited, particularly in Central and Eastern Europe, where access to therapy has recently expanded through national reimbursement programs. Methods This study objective was to evaluate treatment tolerability, hepatic safety, and persistence with Tolvaptan therapy in Romanian patients with rapidly progressive ADPKD. This retrospective single-center study included adults with ADPKD (Mayo classes 1C–1E) treated with Tolvaptan between February 2022 and August 2025. Clinical, biochemical, and imaging data were collected from medical records. The primary endpoint was treatment tolerability, defined by discontinuation rates and causes of withdrawal. Secondary endpoints included hepatic enzyme elevations, aquaretic symptoms, and dose distribution. Exploratory analyses described changes in eGFR and total kidney volume (TKV) at 12 months. Results Of 112 patients who initiated Tolvaptan, 19 (17%) discontinued therapy. Adverse events accounted for 42% of discontinuations, while 58% were due to non-medical reasons (administrative barriers, loss to follow-up). Among evaluable patients at 12 months (n = 44), 81.8% remained on 60/30 mg and 15.9% on 90/30 mg. Hepatic cytolysis occurred in 33.9% of patients, typically mild and frequently associated with concomitant potentially hepatotoxic factors; only two cases exceeded 3× ULN, with full recovery after temporary interruption. Mean urine output at 12 months was 5.2 L/day (SD 1.8). Exploratory assessments showed stable eGFR (67.5→68.4 mL/min/1.73 m²) and an 8.6% increase in TKV. Conclusions Tolvaptan demonstrated acceptable real-world tolerability in this Romanian cohort, with most discontinuations related to aquaretic effects rather than hepatotoxicity. Hepatic abnormalities were generally moderate and reversible. This study provides the first region-specific safety data from Central and Eastern Europe and underscores the importance of structured monitoring and patient education to optimize long-term adherence.