Recent Advances in the GREASE II Study

Background: Autosomal Dominant Polycystic Kidney Disease is a systemic genetic disorder characterized by the progressive formation and enlargement of renal cysts, often leading to end-stage kidney disease.Caloric restriction and ketogenic diet, which promote ketosis and reduce glucose availability, have shown potential in slowing disease progression.Emerging evidence highlights weight loss and visceral fat reduction as important contributors to slower kidney volume growth and better renal outcomes Methods: The Grease II study is a phase II, 24month, randomized, parallel-group, two-arm superiority trial with a 1:1 allocation ratio. It aims to evaluate the efficacy of a ketogenic diet(Modified Atkins Diet–MAD) compared to a balanced normocaloric diet(BND) in 92 patients with rapidly progressive ADPKD.The primary outcome is the difference in kidney volume enlargement between the two groups, assessed by MRI at baseline and after 13months.To minimize potential bias due to glycogen depletion associated with the ketogenic diet, MRIs will be performed after a 30day switch to the BND in both groups Results: To date 40patients were allocated, 7patients have completed the 13month MRI assessment: 4patients were assigned to the BNDgroup and 3to the MADgroup.Preliminary data analysis(per-protocol), as illustrated in panelA, suggest that kidney volume in the MADgroup remains stable over time, in contrast to the expected progressive enlargement typically observed in ADPKD, as seen in the BNDgroup.Additionally, as shown in panelsC and D,patients in the MADgroup exhibited a measurable reduction in both subcutaneous and visceral adipose tissue, consistent with the metabolic effects of carbohydrate restriction Conclusion: Due to the paucity of available data at this stage of the trial, no definitive conclusions can be drawn.Continued recruitment and follow-up are essential to validate these early observations and assess efficacy and safety of the intervention.Minister of HealtRF-2021-12374522 Funding: Government Support – Non-U.S.