Sadrija Cukoski, Adrian Kühn, Christoph Heinrich Lindemann, Sita Arjune, Franziska Meyer, Thomas Schömig, Nils Große-Hokamp, Johannes Schmidt, Philipp Antczak, Thomas Weimbs, Franziska Grundmann and Roman-Ulrich Mueller

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure, with limited treatment options beyond Tolvaptan, which is often accompanied by side effects like hepatotoxicity and polyuria. Emerging research highlights the potential of ketogenic dietary interventions (KDIs) to address the metabolic inflexibility and glucose dependence of cyst-lining epithelial cells in ADPKD. The KETO-ADPKD trial, a randomized controlled study involving 66 patients, explored the feasibility and impact of KDIs and water fasting compared to standard care. Results showed a significant reduction in height-adjusted total kidney volume (htTKV) in patients achieving higher ketone thresholds, confirming the role of ketosis in slowing disease progression. Notably, ketosis, rather than caloric restriction, moderated these effects. These findings underscore the promise of KDIs as a novel, non-pharmacological strategy for managing ADPKD and emphasize the importance of adherence to achieve therapeutic benefits.