Estimation of Changes in Kidney Volume Growth Rate in Autosomal Dominant Polycystic Kidney Disease

Abstract Introduction In Mayo Imaging Classification (MIC) for autosomal dominant polycystic kidney disease (ADPKD), height-adjusted total kidney volume (HtTKV) growth rate is estimated for classification. Estimated HtTKV slope, termed as eHTKV-α, is calculated by equation, [HtTKV at age t]=K(1+α/100)(t-A), where K=150 and A=0 are used in MIC. If eHTKV-α is nearly stable during standard-of-care period, the change in eHTKV-α from baseline can be used for estimation of treatment effect on HtTKV slope. Methods Constancy of eHTKV-α (A=0 and K=150) was evaluated using 453 placebo-assigned subjects in TEMPO 3:4. A and K were sought out respectively, by converged pattern of regression lines of log10(HtTKV) plotted against age for subgroups divided according to MIC, and by change in eHTKV-α from baseline. 239 standard-of-care patients from Kyorin University Cohort (KUC) were served for validation. Changes in eHTKV-α from baseline were evaluated in 809 tolvaptan-treated subjects in TEMPO 3:4. Results In placebo-assigned subjects, eHTKV-α (A=0 and K=150) changed significantly from baseline at third year. As regression lines of placebo-assigned subgroups converged around age 0, A was set as 0, which was confirmed by KUC. K=130 was selected because of minimal change in eHTKV-α from baseline. KUC validated constancy of eHTKV-α (A=0 and K=130) but not that of eHTKV-α (A=0 and K=150). In tolvaptan-treated subjects, eHTKV-α remained significantly lower level than baseline for three years. Conclusions eHTKV-α (A=0 and K=130) was nearly stable from baseline through follow-up in standard-of-care adults. Treatment effects on HtTKV slope can be estimated by changes in eHTKV-α from baseline.