Real-world evidence for using urine osmolality as a practical tool in tolvaptan dose optimization in patients with...

The aim of this prospective single-center study was to evaluate the role of morning urine and 24-hour urine osmolality as biomarkers for guiding individualized dosing of tolvaptan in adults with rapidly progressive autosomal dominant polycystic kidney disease (ADPKD), with the aim of minimizing treatment discontinuations and adverse events.

24 patients (13 men, 11 women; aged 21 - 54 years) received tolvaptan for 7 - 50 months. Dosing was titrated based on tolerability and achievement of urine osmolality ≤ 250 mOsm/kg, measured by freezing point osmometry in both morning spot and 24-hour urine samples.

16 patients (66.7%) remained on 45/15 mg, 7 (29%) required 60/30 mg, and 1 patient (4%) escalated to 90/30 mg of tolvaptan. Morning urine osmolality decreased significantly from 404 ± 231 mOsm/kg to 153 ± 61 mOsm/kg (p < 0.001), and 24-hour urine osmolality was maintained at ≤ 250 mOsm/kg in all patients. No significant differences in osmolality were observed between the patients on 45/15 mg and 60/30 mg. Mild liver enzyme elevations occurred in 9% of 504 total measurements, with 1 patient discontinuing treatment due to a 3-fold rise in transaminases. Another patient discontinued treatment due to aquaretic side effects.

Urine osmolality is a practical and effective biomarker for guiding individualized tolvaptan titration in patients with ADPKD. This approach enabled adequate vasopressin suppression and was associated with a low discontinuation rate, supporting its use in real-world clinical practice.