Long-Term Efficacy of Tolvaptan in ADPKD

At present, tolvaptan is the only therapy available to ameliorate disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD). Tolvaptan is a vasopressin V2 receptor antagonist. There is little data available on real-life outcomes with tolvaptan, and previous study findings are limited by small study sizes, short follow-up periods, or lack of control groups.

Paul Geertsema, MD, and colleagues conducted a study designed to examine the long-term effect of tolvaptan on kidney function and growth in patients with ADPKD compared with controls. The study also assessed determinants of long-term treatment efficacy. The control group included patients with ADPKD who were not treated with tolvaptan.

The study utilized pooled data from the prospective DIPAK cohort and the retrospective OBSERVA cohort. Researchers measured total kidney volume (TKV) every 3 years and estimated glomerular filtrate rate (eGFR) yearly. Acute slope end points were analyzed as treatment effects from tolvaptan initiation to 6 weeks, and chronic slope end points were analyzed following the initial 6 weeks of treatment.

The total analysis cohort included 615 patients; of those, 105 were treated with tolvaptan. The mean age in the overall cohort was 48 years, and 58.2% were female. The average duration of treatment was 6.1 years. The matched analysis cohort included 92 patients in each group (treated and non-treated).

During chronic slope, there was a 14.0% decline in eGFR (–4.36 to –3.75 mL/min/1.73m²/year; P=0.03) in the tolvaptan group compared with a decrease of 1.0% (–4.16 to –4.12 mL/min/`1.73 m2/year; P=0.9) in the control group. There was no significant change in long-term total kidney volume (TKV) growth during the tolvaptan treatment period. The tolvaptan treatment effect was greater among a subgroup of patients with a higher mean osmolar intake.

“In this study, with real-life patient data, long-term follow-up, and a well-matched control group, we found that tolvaptan attenuated long-term kidney function decline but seemed not to influence kidney growth,” the researchers said.

Source: Geertsema P, et al. Nephrol Dial Transplant. doi:10.1093/ndt/gfaf048