Initial eGFR Changes Predict Response to Tolvaptan in ADPKD.

KEY POINTS: This post hoc analysis of the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 study investigated the long-term predictive potential of initial changes in eGFR. Initial eGFR change from baseline to week 3 proved to be a significant and independent indicator of the long-term effects of tolvaptan. No correlation was found between the initial change in eGFR and the annual rate of percent growth in total kidney volume.

BACKGROUND

Tolvaptan, the only pharmaceutical treatment available for autosomal dominant polycystic kidney disease (ADPKD), reduced the rates of total kidney volume (TKV) increase and kidney function decline in patients with ADPKD in the global phase 3 Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 study. Since tolvaptan initiation is associated with an initial decline in the eGFR, this post hoc analysis of the TEMPO 3:4 study investigated whether initial changes in eGFR from baseline to week 3 after tolvaptan administration can predict its longer-term effects on eGFR and TKV in patients with ADPKD.

METHODS

eGFR was estimated using the CKD Epidemiology Collaboration equation at baseline and up to month 36. TKV was estimated using standardized kidney magnetic resonance imaging at baseline and after 12, 24, and 36 months of tolvaptan treatment. The effect of tolvaptan on kidney function and kidney volume was evaluated by measuring changes in eGFR from week 3 and TKV from baseline up to 36 months. All 961 patients randomized to receive tolvaptan in TEMPO 3:4 were included in this analysis.

RESULTS

Initial change in eGFR from baseline to week 3 was a significant and independent predictor of the mean rate of change in eGFR per year. By contrast, there was no association between initial change in eGFR and the rate of percent growth in TKV per year.

CONCLUSIONS

Changes in eGFR after 3 weeks of treatment are likely due to the pharmacologic effect of tolvaptan, and these initial changes are predictive of the long-term effects of tolvaptan treatment.