Risk Profile Improved With Tolvaptan for ADPKD

Among patients with autosomal dominant polycystic kidney disease (ADPKD), the expected rate of decline in estimated glomerular filtration rate (eGFR) is calculated using the 2015 ADPKD  risk classification system developed by Irazabal et al. The system is based on patient height-adjusted kidney volume (htTKV) and age. Patients with typical image findings on MRI (class 1) can be categorized for anticipated slope of eGFR decline from slow progressors (subclass 1A) through rapid progressors (subclass 1E).

For most, but not all patients, subclass assignment remains stable over time, dependent on htTKV growth. Neera K. Dahl, MD, PhD, and colleagues performed an analysis of data from the TEMPO 3:4 trial to examine the effects of tolvaptan on ADPKD risk subclass over time. Results of the analysis were reported during a poster session at the American Society of Nephrology Kidney Week 2022 in a poster titled 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.

The post hoc analysis was designed to compare changes in risk subclass between patients randomized to tolvaptan or placebo. Baseline MRI and age were used to identify patients in subclasses 1B to 1E. The Cochran-Mantel-Haenszel mean score statistic was used compare the proportions of participants (completers only) in both treatment arms in each baseline subclass who shifted to a different subclass over 36 months.

Most of the participants in the TEMPO 3:4 placebo arm remained in their baseline subclass; some progressed to a higher risk subclass and a smaller proportion dropped into a lower risk subclass. In the tolvaptan arm, the proportion of participants who progressed to a higher risk subclass was smaller than the proportion of participants who dropped into a lower risk subclass.

In baseline subclasses 1C and 1D, participants in the placebo arm were statistically more likely to progress to a higher risk subclass than those in the tolvaptan arm subclasses 1C (P<.001) and 1D (P=.0087).

In summary, the researchers said, “Reduction of htTKV growth by tolvaptan in ADPKD improved the population risk profile during the 3-year period of treatment with tolvaptan or placebo.”

Source: Dahl NK, Chebib FT, Rahbari-Oskoui FF et al. Tolvaptan modified patient risk class distribution over time in autosomal dominant polycystic kidney disease (ADPJD): an analysis of data from the TEMPO 3:4 trial. Th-PO413. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2022; November 3, 2022; Orlando, Florida. Funding was provided by Otsuka Pharmaceutical Development & Commercialization Inc.