Estimation of Changes in Kidney Volume Growth Rate in ADPKD

Eiji Higashihara; Hiroshi Fukuhara; John Ouyang; Jennifer Lee; Kikuo Nutahara; Mistuhiro Tanbo; Tsuyoshi Yamaguchi; Satoru Taguchi; Satoru Muto; Shinya Kaname; Isao Miyazaki; Shigeo Horie

doi:10.1016/j.ekir.2020.06.011

Estimation of Changes in Kidney Volume Growth Rate in ADPKD

Kidney Int Rep. 2020 Jun 20;5(9):1459-1471. doi: 10.1016/j.ekir.2020.06.011. eCollection 2020 Sep.

Authors

Affiliations

¹ Department of Hereditary Kidney Disease Research, Kyorin University School of Medicine, Tokyo, Japan.
² Department of Urology, Kyorin University School of Medicine, Tokyo, Japan.
³ Otsuka Pharmaceutical Development and Commercialization, Rockville, Maryland, USA.
⁴ Department of Urology, Juntendo University School of Medicine, Tokyo, Japan.
⁵ Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan.
⁶ Department of Radiology, Kyorin University School of Medicine, Tokyo, Japan.

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-α, is calculated by the 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 a standard-of-care period, the change in eHTKV-α from baseline can be used for estimation of the treatment effect on the HtTKV slope.

Methods: The constancy of eHTKV-α (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-α from baseline. A total of 239 standard-of-care patients from the Kyorin University Cohort (KUC) served as 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 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-α from baseline. The KUC validated the 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 than baseline for 3 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 the HtTKV slope can be estimated by changes in eHTKV-α from baseline.

Keywords: autosomal dominant polycystic kidney disease (ADPKD); biomarker; height-adjusted total kidney volume (HtTKV); tolvaptan; total kidney volume (TKV).