RESET-PKD: A pilot trial on short-term ketogenic interventions in autosomal dominant polycystic kidney disease.

BACKGROUND: Ketogenic dietary interventions (KDI) have been shown to be effective in animal models of polycystic kidney disease, but data from clinical trials are lacking.

METHODS: Ten ADPKD patients with rapid disease progression were enrolled at visit V1 and initially maintained a carbohydrate (CHO)-rich diet. At V2, patients entered one of the two KDI arms: a 3-day water fast (WF) or a 14-day ketogenic diet (KD). At V3, they resumed their normal diet for 3 to 6 weeks until V4. At each visit, MRI kidney and liver volumetry was performed. Ketone bodies were evaluated to assess metabolic efficacy and questionnaires were used to determine feasibility.

RESULTS: All participants (KD n = 5, WF n = 5; age 39.8 ± 11.6 years; eGFR 82 ± 23.5 ml/min; total kidney volume (TKV) 2224 ± 1156 ml) were classified as Mayo Class 1C to 1E. Acetone levels in breath and BHB blood levels increased in both study arms (V1 to V2 average acetone: 2.7±1.2 ppm, V2 to V3: 22.8±11.9 ppm, p = 0.0006; V1 to V2 average BHB: 0.22±0.08 mmol/l, V2 to V3: 1.88±0.93 mmol/l, p = 0.0008). 9/10 patients reached a ketogenic state and 9/10 evaluated KDIs as feasible. TKV did not change during this trial. However, we found a significant impact on total liver volume (ΔTLV V2 to V3: -7.7%, p = 0.01), mediated by changes in its non-cystic fraction.

CONCLUSIONS: RESET-PKD demonstrates that short-term KDIs potently induce ketogenesis and are feasible for ADPKD patients in daily life. While TLV quickly changed upon the onset of ketogenesis, changes in TKV may require longer-term interventions.