Estimation of Changes in Kidney Volume Growth Rate in ADPKD

Introduction: In the Mayo Imaging Classification (MIC) for autosomal dominant polycystic kidney disease (ADPKD), the height-adjusted total kidney volume (HtTKV) growth rate is estimated for classification. Estimated HtTKV slope, termed as eHTKV-alpha, is calculated by the equation [HtTKV at age t] = K(1+alpha/100)((t-A)), where K = 150 and A = 0 are used in MIC. If eHTKV-alpha is nearly stable during a standard-of-care period, the change in eHTKV-alpha from baseline can be used for estimation of the treatment effect on the HtTKV slope. Methods: The constancy of eHTKV-alpha (A = 0 and K = 150) was evaluated using 453 placebo-assigned subjects in the Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4 trial. A and K were sought out respectively by a converged pattern of regression lines of log10(HtTKV) plotted against age for subgroups divided according to MIC, and by change in eHTKV-alpha from baseline. A total of 239 standard-of-care patients from the Kyorin University Cohort (KUC) served as validation. Changes in eHTKV-alpha from baseline were evaluated in 809 tolvaptan-treated subjects in TEMPO 3:4. Results: In placebo-assigned subjects, eHTKV-alpha (A = 0 and K = 150) changed significantly from baseline at the 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-alpha from baseline. The KUC validated the constancy of eHTKV-alpha (A = 0 and K = 130) but not that of eHTKV-alpha (A=0 and K=150). In tolvaptan-treated subjects, eHTKV-alpha remained significantly lower than baseline for 3 years. Conclusions: eHTKV-alpha (A = 0 and K = 130) was nearly stable from baseline through follow-up in standard-of-care adults. Treatment effects on the HtTKV slope can be estimated by changes in eHTKV-alpha from baseline. (C) 2020 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).