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

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. 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. 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.