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

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          Background: Tolvaptan was approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD). However, the official indication of “rapidly progressive disease” is described differently in the clinical guidelines. We aim to define “rapidly progressive disease” by risk of ESRD, which is evaluated using estimated height-adjusted total kidney volume (HtTKV) growth rate. Methods: The risk of ESRD was retrospectively analyzed in 617 initially non-ESRD adults with ADPKD and observed with standard of care between 2007 and 2018. The estimated annual growth rate of the HtTKV, termed as eHTKV-α (%/year), is derived from the following equation: [HtTKV at age t] = K(1 + eHTKV-α/100)<sup> t</sup>, where K = 150 mL/m is used in Mayo Imaging Classification and K = 130 mL/m is proposed for individually stable eHTKV-α value from baseline. The accuracy of eHTKV-α to predict ESRD for censored ages was analyzed using time-dependent receiver-operating characteristic curves (ROC). The cutoff point of initially measured eHTKV-α to predict ESRD was assessed using Kaplan-Meier and Cox’s proportional hazards models. Performance characteristics of the cutoff point for censored ages were calculated using time-dependent ROC and validated by the bootstrap method. Results: The area under the time-dependent ROC of eHTKV-α to predict ESRD at age 65 was 0.89 ± 0.04 ( K = 130). The mean renal survival was less than 70 years at eHTKV-α ≥4.0%/year ( K = 130). Mean renal survival was approximately 12 years shorter, and hazard ratio of ESRD was more than 5-time higher at this cutoff point than at lower point. Time-dependent sensitivity for age 65 and cutoff point of 4.0%/year ( K = 130) was 93.4 ± 0.3%. Between cutoff points ≥4.0%/year ( K = 130) and ≥3.5%/year ( K = 150), there was no significant difference in performance characteristics and accuracy to predict ESRD. Conclusion: eHTKV-α well predicts ESRD. Initially, measured eHTKV-α ≥4.0%/year ( K = 130) defines high-risk ESRD. Without additional conditions, a single eHTKV-α cutoff point identifies subjects that are most likely to benefit from tolvaptan.

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          Most cited references 27

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          Time-Dependent AUC with Right-Censored Data: A Survey

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            A practical guide for treatment of rapidly progressive ADPKD with tolvaptan

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              Mutations in multiple PKD genes may explain early and severe polycystic kidney disease


                Author and article information

                Am J Nephrol
                American Journal of Nephrology
                S. Karger AG
                December 2020
                23 November 2020
                : 51
                : 11
                : 881-890
                aDepartment of Hereditary Kidney Disease Research, Kyorin University School of Medicine, Tokyo, Japan
                bDepartment of Urology, Kyorin University School of Medicine, Tokyo, Japan
                cDepartment of Urology, Juntendo University School of Medicine, Tokyo, Japan
                dDepartment of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan
                eDepartment of Radiology, Kyorin University School of Medicine, Tokyo, Japan
                fBiostatistical Research Co., Ltd., Tokyo, Japan
                Author notes
                *Eiji Higashihara, Department of Hereditary Kidney Disease Research, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611 (Japan),
                511797 Am J Nephrol 2020;51:881–890
                © 2020 The Author(s) Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 2, Tables: 5, Pages: 10
                Patient-Oriented, Translational Research: Research Article


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