Initial eGFR Changes Predict Response to Tolvaptan in ADPKD.

Abstract

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 TEMPO 3:4 study. Since tolvaptan initiation is associated with an initial decline in the estimated glomerular filtration rate (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. eGFR was estimated using the Chronic Kidney Disease 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 were evaluated by measuring changes in eGFR from week 3 and TKV from baseline, up to 36 months. All 961 patients randomised to receive tolvaptan in TEMPO 3:4 were included in this analysis. 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. In contrast, there was no association between initial change in eGFR and the rate of percent growth in TKV per year. 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.