Daily Caloric Restriction in Overweight and Obese Adults with ADPKD: Rationale and Protocol of a Randomized Controlled Trial

INTRODUCTION: Mounting evidence suggests dysregulated metabolism as a feature of autosomal dominant polycystic kidney disease (ADPKD) and that mild-to-moderate food restriction significantly slows cyst growth in murine models. Epidemiological data and a pilot and feasibility study in humans further support that targeting weight and adiposity loss via daily caloric restriction (DCR) is a potential strategy to slow kidney growth in adults with ADPKD and overweight or obesity. METHODS: This is a single site, randomized, single blind (investigator), parallel-group, controlled trial that randomized 120 participants to a 24-month DCR-based behavioral weight loss intervention or control (standard clinical dietary advice for ADPKD) (NCT04907799). The primary outcome is change in height-adjusted total kidney volume by magnetic resonance imaging over a 24-month duration. 84 women and 36 men were randomized, and the study population was 93% Non-Hispanic White. At baseline, mean ± s.d. age was 45 ± 11 years, the mean CKD-EPI eGFR was 68 ± 26 ml/min/1.73m2, and the median (interquartile range) htTKV was 986 (700, 1398) ml/m. Twenty-nine (24%) participants were using tolvaptan at baseline. The final study cohort will be completed in July 2027. CONCLUSIONS: This is the first phase 2, randomized clinical trial targeting caloric restriction in patients with ADPKD, and will provide important insight to the research community, patients, and providers.