INTRODUCTION: This analysis aimed to assess the effect of tolvaptan (TOL) compared with standard of care (SOC) on kidney function in older patients.
METHODS: Subjects aged > 55 years were identified from a large, pooled ADPKD database of subjects receiving TOL or SOC in 11 clinical studies from 2001 to 2018 sponsored by Otsuka or the National Institutes of Health and linked longitudinally across studies to allow long-term follow-up of unique subjects. To minimize confounding effects, TOL subjects were matched 1:1 with SOC subjects on baseline chronic kidney disease (CKD) stage, sex, age (±2 years), and estimated glomerular filtration rate (eGFR) (±5 mL/min/1.73 m2). The annual rate of change of eGFR (CKD-EPI) was estimated using a mixed model that included treatment, time, baseline eGFR, and time-by-treatment interaction. For subjects in the TOL group, the eGFR assessments < 7 days after tolvaptan initiation, during the tolvaptan treatment gap, or after tolvaptan treatment termination were excluded. This conservative analysis approach accounted for potential bias caused by the hemodynamic effect of tolvaptan.
RESULTS: Of 1,137 eligible subjects aged > 55 years, 230 received at least one dose of TOL. After the exclusion of subjects who received TOL only in the titration/run-in phase, 95 subjects (mean age, 60.2 years; age range, 56 to 65 years; 46% male; 69% in CKD stage 3; 31% in CKD stage 4) who were randomized to TOL treatment in the REPRISE clinical trial were included in the matched analysis. The mean duration of TOL was 2.4 years with a mean gap of 22 days between REPRISE and the extension study. The estimated annual rate of decline of eGFR (mL/min/1.73m2) was 2.33 in TOL and 3.99 in SOC. TOL significantly reduced the annual rate of eGFR decline by 1.66 mL/min/1.73 m2 (95% confidence interval, 0.43-2.90; P = 0.009).
CONCLUSIONS: This pooled data analysis highlights efficacy of TOL by slowing kidney function decline in patients with ADPKD between ages 56 and 65 years with CKD stage 3 and 4.
