Tolvaptan in ADPKD beyond trials: a single-center real-world experience

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. This study evaluates treatment tolerability, hepatic safety, and persistence with Tolvaptan therapy in Romanian patients with rapidly progressive ADPKD (Mayo classes 1 C-1E). This retrospective single-center study included adults with ADPKD 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 motivation for withdrawal. Secondary endpoints included elevations in liver enzymes, aquaretic symptoms, and the variability in Tolvaptan dosing regimens. Exploratory analyses described changes in eGFR and total kidney volume (TKV) at 12 months. Out 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 dose. Elevation of liver enzymes 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, from 69.84 mL/min/1.73 m² at baseline to 71.52 mL/min/1.73 m² at 1 year, and an 8.6% increase in TKV. Tolvaptan demonstrated good real-world tolerability in this Romanian cohort, with treatment discontinuation predominantly related to aquaretic effects rather than hepatotoxicity. Liver abnormalities were moderate and reversible. This study provides region-specific real-world safety data on tolvaptan from Central and Eastern Europe and underscores the importance of structured monitoring and patient education to optimize long-term adherence.