# 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

## TL;DR

This study shows that the change in kidney volume growth rate after one year of tolvaptan treatment can predict long-term kidney outcomes in patients with a genetic kidney disease.

## Contribution

The study identifies the 1-year change in eHTKV-α as a novel early biomarker for predicting long-term renal outcomes in ADPKD patients on tolvaptan.

## Key findings

- 1-year percent change in eHTKV-α significantly predicts annual changes in kidney volume and eGFR over 3 years.
- Baseline factors like age, sex, and BMI also influence long-term kidney outcomes.
- Urine osmolality and plasma copeptin levels were not significant predictors of treatment response.

## Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1007/s10157-024-02589-1.