Abstract: SA-PO0577
Urine Osmolality for Individualized Dosing of Tolvaptan in Adults with Rapidly Progressive ADPKD
Session Information
- Cystic Kidney Diseases: Clinical Research
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Author
- Marn Pernat, Andreja, University Medical Center Ljubljana, Ljubljana, Slovenia
Background
The aim of our study was to investigate the potential role of urine osmolality as a biomarker that could help individualize tolvaptan dosing in our cohort of adult patients with ADPKD and rapid disease progression, thus minimizing discontinuation rates and side effects.
Methods
A prospective single-center study of 25 adult patients with rapidly progressing ADPKD was conducted at the nephrology outpatient clinic of UMC Ljubljana, the only specialized center for the treatment of ADPKD with tolvaptan in Slovenia. Data were collected from 13 men and 11 women, aged 21 to 54 years ( 40 ± 9 years old) who were treated with tolvaptan for between 7 and 50 months. The efficacy of tolvaptan was defined as the ability to maintain urine osmolality below 200 mOsm/kg, as measured in the morning urine sample prior to the tolvaptan dose using a freezing point osmometer. The effect of tolvaptan during the day was estimated from the 24-hour urine osmolality with the same 200 mOsm/kg cut-off for dose adjustment. Side effects were monitored during the 4-year follow-up period.
Results
Treatment with tolvaptan was started at a dose of 45/15 mg and gradually increased to a maximum dose of 60/30 mg in 7 patients and 90/30 mg per day in 1 patient, depending on tolerability and urine osmolality. 16 patients had a final dose of 45/15 mg. Polyuria was observed in all patients with an average diuresis of 6100 mL/day (3600–8900). One patient discontinued treatment due to aquaretic effects. The average morning urine osmolality of at baseline was 404 ± 231 and was reduced to 153 ± 61 mOsm/kg by tolvaptan. 24-hour urine osmolality showed a sustained urine osmolality of < 200 mOsm/kg in all patients and averaged 145 ± 27 mOsm/kg. Liver enzymes exceeded the reference value up to twice in 9% of all 504 measurements. Tolvaptan was discontinued in only one patient. No hepatoxicity was observed in 7 (29%) patients.
Conclusion
In this prospective study of adult patients with ADPKD, we found that using a urine osmolality of less than 200 mOsm/kg to titrate tolvaptan therapy results in lower tolvaptan doses, a very low discontinuation rate, and fewer side effects. We believe that urine osmolality, an indicator of vasopressin-2 receptor suppression, could help individualize tolvaptan dosing in clinical practice.
Funding
- Clinical Revenue Support