Change in kidney volume growth rate and renal outcomes of tolvaptan treatment in autosomal dominant polycystic kidney disease: post-hoc analysis of TEMPO 3:4 trial.

Background: Despite of long-lasting tolvaptan treatment, individual renal outcomes are unclear in autosomal dominant polycystic kidney disease (ADPKD). This post-hoc analysis of the TEMPO 3:4 trial aimed to evaluate the predictability of estimated height-adjusted total kidney volume growth rate (eHTKV-α) on renal outcomes.

Methods: In TEMPO 3:4, 1445 patients with ADPKD were randomised to tolvaptan or placebo for 3 years. The present analysis included patients with total kidney volume (TKV) data available at baseline and month 12 (tolvaptan, n = 812; placebo, n = 453); tolvaptan-assigned patients were grouped into quartiles based on percent change in eHTKV-α from baseline at 1 year. Clinical parameters were compared between quartiles, and regression analyses evaluated the predictive value of 1-year percent change in eHTKV-α and other factors on annual changes in TKV and estimated GFR (eGFR) over 3 years.

Results: Trend tests identified significant differences between quartiles for several baseline parameters. Multivariate regression models confirmed that 1-year percent change in eHTKV-α was a significant predictor of annual changes in both TKV and eGFR over 3 years. Other significant predictors of annual changes in TKV and eGFR over 3 years were sex, age and body mass index, and first-year change in eGFR, race and baseline eGFR, respectively. Predicting factors using urine osmolality and plasma copeptin levels were not significant by backward stepwise selection analysis.

Conclusions: 1-year percent change in eHTKV-α is useful biomarker to identify treatment good responders and may be utilized for early estimate of trial outcomes of new drugs in ADPKD.