Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: a multicenter real-life study

Background: Tolvaptan is the only disease-modifying treatment approved to slow kidney disease progression in autosomal dominant polycystic kidney disease (ADPKD). Data on tolvaptan in ADPKD outside of clinical trials are limited, usually deal with short-term observations and are characterized by a drop-out rate of 21%-56%. Methods: In this retrospective, observational, multicenter study enrolling 122 Italian patients with ADPKD and rapid progressive renal disease, we evaluated the tolerability and side effects of tolvaptan treatment in a real-life setting. A personalized treatment strategy, based on an accurate patient selection and a strict clinical and laboratory monitoring, was applied. Results: During a median follow-up of 34.0 (interquartile range 17.3; -46.5) months the overall adherence on tolvaptan was 82.0%. Permanent withdrawal was reported in 22/122 patients (18.0%) after a mean of 34.4 ± 18.0 months; the main reasons for drug permanent withdrawal were onset of kidney failure in 7/122 (5.7%), poor tolerance to aquaresis in 4/122 (3.3%), family planning in 3/122 (2.5%) and liver function test elevation in 2/122 patients (1.6%). Temporary discontinuation was observed in 35/122 patients (28.7%) and in most cases it was not related to drug side effects. In order to evaluate tolvaptan eligibility, historic estimated glomerular filtration rate decline was the most inclusive criteria (92.9%) when compared with Mayo Imaging Classification (89.7%) and Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) Score (22.6%). Conclusion: This real-life study confirms the feasibility, safety, and tolerability of tolvaptan treatment. In order to overcome the challenges of tolvaptan treatment, our experience suggests that a dedicated PKD team may play a key role in implementing strategies focused to reduce drop-out and achieve treatment success.