Abstract
INTRODUCTION: Tolvaptan has been shown to reduce renal volume and delay disease progression in autosomal-dominant polycystic kidney disease (ADPKD). However, no biomarkers are currently available to guide dose adjustment. We aimed to explore the possibility of individualized tolvaptan dose adjustments based on cut-off values for urinary osmolality (OsmU). METHODS: This prospective cohort study included patients with ADPKD, with rapid disease progression. Tolvaptan treatment was initiated at a dose of 45/15 mg and increased based on OsmU, with a limit set at 200 mOsm/kg. Primary renal events (25% decrease in estimated glomerular filtration rate [eGFR] during treatment), within-patient eGFR slope, and side effects were monitored during the 3-year follow-up. RESULTS: Forty patients participated in the study. OsmU remained below 200 mOsm/kg throughout the study period, and most patients required the minimum tolvaptan dose (mean dose, 64 [±10] mg), with a low discontinuation rate (5%). The mean annual decline in eGFR was -3.05 (±2.41) ml/min per 1.73 m(2) during tolvaptan treatment, compared to the period preceding treatment, corresponding to a reduction in eGFR decline of more than 50%. Primary renal events occurred in 20% of patients (mean time to onset, 31 months; 95% confidence interval [CI] = 28-34). CONCLUSION: Individualized tolvaptan dose adjustment based on OsmU in patients with ADPKD and rapid disease progression provided benefits in terms of reducing eGFR decline, compared with reference studies, and displayed lower dropout rates and fewer side effects. Further studies are required to confirm optimal strategies for the use of OsmU for tolvaptan dose adjustment in patients with ADPKD.