Edwards ME, et al. - Given tolvaptan slowed the decline of eGFR in patients with autosomal dominant polycystic kidney disease at early and later stages of CKD, respectively, in the 3-year Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4 and 1-year Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trials, researchers investigated if the reduction related to treatment with tolvaptan was sustained, cumulative, and likely to delay the requirement for kidney replacement therapy. At the end of 11.2 years (average 4.6 years) of follow-up, they found that treatment with tolvaptan resulted in a sustained reduction in the annual rate of eGFR decline in patients, vs controls. They also observed an increasing separation of eGFR values over time between the two groups.

Methods

• Clinical trials of tolvaptan were conducted at the Mayo Clinic, including a total of 128 patients with autosomal dominant polycystic kidney disease.
• These patients were enrolled into open-label extension studies; 20 participated in short-term studies or received placebo only, while, safety analysis was performed including the remaining 108.
• Efficacy analysis was carried out in 97 patients treated with tolvaptan for ≥1 year (mean±SD, 4.6±2.8; range, 1.1–11.2), by using three approaches: comparison of eGFR slopes and outcome (33% reduction from baseline eGFR) to controls matched by sex, age, and baseline eGFR; stability of eGFR slopes with duration of follow-up; and comparison of observed and predicted eGFRs at last follow-up.

Results

• They found lower eGFR slopes from baseline (mean±SD, -2.20±2.18 ml/min per 1.73 m² per year) and from month 1 (mean±SD, -1.97±2.44 ml/min per 1.73 m² per year) were exhibited by patients treated with tolvaptan, vs controls (mean±SD, -3.50±2.09 ml/min per 1.73 m²per year; P<0.001).
• Findings demonstrated that patients treated with tolvaptan also had a lower risk of a 33% reduction in eGFR (risk ratio, 0.63; 95% confidence interval, 0.38 to 0.98 from baseline; risk ratio, 0.53; 95% confidence interval, 0.31 to 0.85 from month 1).
• During follow-up, patients treated with tolvaptan did not show change in annualized eGFR slopes, and differences between observed and predicted eGFRs at last follow-up increased with duration of treatment.