Estimation of Changes in Kidney Volume Growth Rate in ADPKD

Abstract

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-a, is calculated by the equation [HtTKV at age t] ¼ K(1þa/100) (t-A) , where K ¼ 150 and A ¼ 0 are used in MIC. If eHTKV-a is nearly stable during a standard-ofcare period, the change in eHTKV-a from baseline can be used for estimation of the treatment effect on the HtTKV slope. Methods: The constancy of eHTKV-a (A ¼ 0 and K ¼ 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-a from baseline. A total of 239 standard-of-care patients from the Kyorin University Cohort (KUC) served as validation. Changes in eHTKV-a from baseline were evaluated in 809 tolvaptan-treated subjects in TEMPO 3:4. Results: In placebo-assigned subjects, eHTKV-a (A ¼ 0 and K ¼ 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 ¼ 130 was selected because of minimal change in eHTKV-a from baseline. The KUC validated the constancy of eHTKV-a (A ¼ 0 and K ¼ 130) but not that of eHTKV-a (A¼0 and K¼150). In tolvaptan-treated subjects, eHTKV-a remained significantly lower than baseline for 3 years. Conclusions: eHTKV-a (A ¼ 0 and K ¼ 130) was nearly stable from baseline through follow-up in standardof-care adults. Treatment effects on the HtTKV slope can be estimated by changes in eHTKV-a from baseline.

Imaging Identification of Rapidly Progressing Autosomal Dominant Polycystic Kidney Disease: Simple Eligibility Criterion for Tolvaptan

“…eHTKV-α, estimated height-adjusted total kidney volume growth rate α (%/year); SE, standard error; CI, confidence interval. DOI: 10.1159/000511797 ment of kidney volume and height [6,17]. eHTKV-α is a good renal prognostic biomarker [6], which is confirmed by a high validated AUC of eHTKV-α for predicting ESRD in this study (Table 2; Fig.…”

“…A total of 617 standard-of-care patients with typical ADPKD and baseline age above 19 who visited Kyorin University Hospital (388 patients) and Juntendo University Hospital (229 patients) between April 2007 and December 2018 were analyzed. Subjects under the age of 20 were excluded because the equation for eHTKV-α is derived from the analysis of adult data [6, 17]. Patients who started RRT prior to the initial visit or who received invasive therapy or tolvaptan to reduce the renal volume at any time were excluded from the analysis.…”

“…The Mayo Class was proposed as a simple model to predict renal prognosis in adults with typical ADPKD. The Mayo Class is distinguished using the estimated height-adjusted TKV (HtTKV) growth rate (%/year), which was abbreviated as eHTKV-α [17]. eHTKV-α is calculated using the following equation: [HtTKV at age t ] = K × (1 + eHTKV-α/100) t , where K = 150 mL/m is used [6].…”

“…The constancy of individual eHTKV-α over years is preferable for prognostic application of eHTKV-α. In our previous study, K = 130 mL/m yielded a more stable individual eHTKV-α from baseline [17].…”

Estimating Growth Rate by a Single Measurement of Kidney Volume in ADPKD

“…Using the TEMPO 3:4 dataset for a development set and Kyorin University cohort for a validation set, Higashihara et al. 6 investigated the constancy of eHTKV-α, which was assumed to be stable in MIC. In placebo-assigned subjects in TEMPO 3:4, when A = 0 and K = 150, eHTKV-α fluctuated significantly from baseline during 3 years of observation.…”