Feasibility and impact of ketogenic dietary interventions in polycystic kidney disease: KETO-ADPKD-a randomized controlled trial.

Sadrija Cukoski, Christoph Heinrich Lindemann, Sita Arjune, Polina Todorova, Theresa Brecht, Adrian Kühn, Simon Oehm, Sebastian Strubl, Ingrid Becker, Ulrike Kämmerer, Jacob Alexander Torres, Franziska Meyer, Thomas Schömig, Nils Große Hokamp, Florian Siedek, Ingo Gottschalk, Thomas Benzing, Johannes Schmidt, Philipp Antczak, Thomas Weimbs, Franziska Grundmann, Roman-Ulrich Müller

Journal: Cell reports. Medicine 2023;4(11):101283

PMID: 37935200

Free Full Text on Elsevier Science View on PubMed

Plain Language Summary

Autosomal-dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the growth of numerous cysts in the kidneys, leading to kidney failure over time. Dietary interventions, such as the ketogenic diet (KD), have been explored for their potential to improve kidney function and overall health in ADPKD patients. The aim of this study was to assess the feasibility and impact of ketogenic dietary interventions on kidney function and related health outcomes in patients with ADPKD. This study was a randomised controlled trial involving 66 patients with ADPKD, divided into three groups: a ketogenic diet group, a water fasting group, and a control group following standard dietary recommendations. Results showed that ketogenic dietary interventions are feasible and may offer significant health benefits for patients with ADPKD, including improved kidney function, reduced body weight, and alleviated symptoms. Authors concluded that further long-term studies are needed to confirm the sustainable benefits and safety of the ketogenic diet for ADPKD patients. However, the findings of these studies provide a basis for improved counselling of patients with ADPKD choosing to be on a KD for personal motivation.

Abstract

Ketogenic dietary interventions (KDIs) are beneficial in animal models of autosomal-dominant polycystic kidney disease (ADPKD). KETO-ADPKD, an exploratory, randomized, controlled trial, is intended to provide clinical translation of these findings (NCT04680780). Sixty-six patients were randomized to a KDI arm (ketogenic diet [KD] or water fasting [WF]) or the control group. Both interventions induce significant ketogenesis on the basis of blood and breath acetone measurements. Ninety-five percent (KD) and 85% (WF) report the diet as feasible. KD leads to significant reductions in body fat and liver volume. Additionally, KD is associated with reduced kidney volume (not reaching statistical significance). Interestingly, the KD group exhibits improved kidney function at the end of treatment, while the control and WF groups show a progressive decline, as is typical in ADPKD. Safety-relevant events are largely mild, expected (initial flu-like symptoms associated with KD), and transient. Safety assessment is complemented by nuclear magnetic resonance (NMR) lipid profile analyses.

Address: Department II of Internal Medicine and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.; Department II of Internal Medicine and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Center for Rare Diseases Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Cologne Cluster of Excellence on Cellular Stress Responses in Ageing-Associated Diseases, Cologne, Germany.; Department II of Internal Medicine and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Department of Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA, USA.; Institute of Medical Statistics and Computational Biology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.; Department of Obstetrics and Gynecology, University Hospital of Würzburg, Würzburg, Germany.; Department of Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA, USA.; University of Cologne, Faculty of Medicine and University Hospital, Institute of Diagnostic and Interventional Radiology, Cologne, Germany.; University of Cologne, Faculty of Medicine and University Hospital, Division of Prenatal Medicine, Department of Obstetrics and Gynecology, Cologne, Germany.; Department II of Internal Medicine and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Bonacci GmbH, Cologne, Germany.; Department II of Internal Medicine and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Cologne Cluster of Excellence on Cellular Stress Responses in Ageing-Associated Diseases, Cologne, Germany.; Department II of Internal Medicine and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Center for Rare Diseases Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Cologne Cluster of Excellence on Cellular Stress Responses in Ageing-Associated Diseases, Cologne, Germany. Electronic address: [email protected].

DOI: 10.1016/j.xcrm.2023.101283