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

doi:10.1016/j.xcrm.2023.101283

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

Cell Rep Med. 2023 Nov 21;4(11):101283. doi: 10.1016/j.xcrm.2023.101283. Epub 2023 Nov 7.

Authors

Sadrija Cukoski¹, Christoph Heinrich Lindemann¹, Sita Arjune², Polina Todorova¹, Theresa Brecht¹, Adrian Kühn¹, Simon Oehm¹, Sebastian Strubl³, Ingrid Becker⁴, Ulrike Kämmerer⁵, Jacob Alexander Torres⁶, Franziska Meyer⁷, Thomas Schömig⁷, Nils Große Hokamp⁷, Florian Siedek⁷, Ingo Gottschalk⁸, Thomas Benzing², Johannes Schmidt⁹, Philipp Antczak¹⁰, Thomas Weimbs⁶, Franziska Grundmann¹, Roman-Ulrich Müller¹¹

Affiliations

¹ Department II of Internal Medicine and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
² 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.
³ 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.
⁴ Institute of Medical Statistics and Computational Biology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
⁵ Department of Obstetrics and Gynecology, University Hospital of Würzburg, Würzburg, Germany.
⁶ Department of Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA, USA.
⁷ University of Cologne, Faculty of Medicine and University Hospital, Institute of Diagnostic and Interventional Radiology, Cologne, Germany.
⁸ University of Cologne, Faculty of Medicine and University Hospital, Division of Prenatal Medicine, Department of Obstetrics and Gynecology, Cologne, Germany.
⁹ 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.
¹⁰ 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.
¹¹ 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: roman-ulrich.mueller@uk-koeln.de.

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.

Keywords: ADPKD; cholesterol; ketogenic diet; ketosis; kidney; lipids; low carb; nutrition; polycystic kidney disease; water fasting.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Diet, Ketogenic*
Feasibility Studies
Humans
Liver
Magnetic Resonance Imaging
Polycystic Kidney, Autosomal Dominant* / complications
Polycystic Kidney, Autosomal Dominant* / drug therapy

Associated data

ClinicalTrials.gov/NCT04680780