Kidney Week

Abstract: TH-PO413

Tolvaptan Modifies Patient Risk Class Distribution Over Time in Autosomal Dominant Polycystic Kidney Disease (ADPKD): An Analysis of Data From the TEMPO 3:4 Trial

Session Information

• Genetic Diseases of the Kidneys: Cystic - I
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1101 Genetic Diseases of the Kidneys: Cystic

Authors

• Dahl, Neera K., Yale School of Medicine, New Haven, Connecticut, United States

Neera K. Dahl,

• Chebib, Fouad T., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Fouad T. Chebib,

• Rahbari-Oskoui, Frederic F., Emory University School of Medicine, Atlanta, Georgia, United States

Frederic F. Rahbari-Oskoui,

• Japes, Hina, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, New Jersey, United States

Hina Japes,

• Jiang, Huan, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, New Jersey, United States

Huan Jiang,

• Tracy, LaRee A., Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, New Jersey, United States

LaRee A. Tracy,

• Mccormick, Linda, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, New Jersey, United States

Linda Mccormick,

• Maringer, Katherine, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, New Jersey, United States

Katherine Maringer,

• Perrone, Ronald D., Tufts Medical Center, Boston, Massachusetts, United States

Ronald D. Perrone,

• Nourbakhsh, Ali, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, New Jersey, United States

Ali Nourbakhsh,

Background

The ADPKD risk classification system developed by Irazabal et al (J Am Soc Nephrol 2015;26:160) estimates the expected rate of eGFR decline based on patient height-adjusted total kidney volume (htTKV) and age. Patients with typical imaging findings on MRI (class 1) can be categorized for their anticipated slope of eGFR decline from slow progressors (subclass 1A) through rapid progressors (subclass 1E). Subclass assignment remains stable over time for most, but not all patients, dependent on htTKV growth. To evaluate effects of tolvaptan on ADPKD risk subclass over time, we analyzed data from the TEMPO 3:4 trial.

Methods

A post hoc analysis compared changes in risk subclass between subjects randomized to tolvaptan or placebo. Subjects in subclasses 1B-1E were identified from baseline MRI and age. The proportions of subjects (completers only) in each baseline subclass who shifted to a different subclass over 36 months were compared using a Cochran-Mantel-Haenszel mean score statistic for association between treatment groups.

Results

Consistent with earlier findings by Irazabal et al, most subjects in the TEMPO 3:4 placebo arm remained in their baseline subclass, with some progressing to a higher risk subclass and a smaller proportion dropping into a lower risk subclass (Figure). In the tolvaptan arm, by contrast, the proportion who progressed to a higher risk subclass was smaller than that who dropped into a lower risk subclass. Subjects receiving placebo were statistically more likely to progress to a higher risk subclass than those receiving tolvaptan in baseline subclasses 1C (P<0.0001) and 1D (P=0.0087).

Conclusion

Reduction of htTKV growth by tolvaptan in ADPKD improved the population risk profile during the 3-year period of treatment with tolvaptan or placebo.

Figure. Shift in ADPKD risk subclass to month 36 by baseline subclass and treatment arm

Funding

• Commercial Support –