Kidney Week

Abstract: TH-PO987

KETO-ADPKD: A Randomized, Controlled Trial on Ketogenic Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease

Session Information

• Late-Breaking Clinical Trials (Posters)
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1101 Genetic Diseases of the Kidneys: Cystic

Authors

• Cukoski, Sadrija, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Sadrija Cukoski,

• Lindemann, Christoph Heinrich, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Christoph Heinrich Lindemann,

• Brecht, Theresa, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Theresa Brecht,

• Kühn, Adrian, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Adrian Kühn,

• Arjune, Sita, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Sita Arjune,

• Todorova, Polina, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Polina Todorova,

• Meyer, Franziska Inka, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Franziska Inka Meyer,

• Siedek, Florian, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Florian Siedek,

• Antczak, Philipp, Universitat zu Koln, Cologne, Nordrhein-Westfalen, Germany

Philipp Antczak,

• Gottschalk, Ingo, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Ingo Gottschalk,

• Weimbs, Thomas, University of California Santa Barbara, Santa Barbara, California, United States

Thomas Weimbs,

• Grundmann, Franziska, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Franziska Grundmann,

• Mueller, Roman-Ulrich, Uniklinik Koln, Cologne, Nordrhein-Westfalen, Germany

Roman-Ulrich Mueller,

Background

ADPKD animal models revealed a potent beneficial effect of ketogenic dietary interventions (KDIs).

Methods

63 ADPKD patients were randomized to 3 months of ketogenic diet (KD), monthly 3-day water fasting (WF) or ad libitum diet (Control). The primary endpoint was a feasibility analysis combining a questionnaire and metabolic efficacy (blood β-Hydroxybutyric acid (BHB), breath acetone), to be reached by ≥75% in each group. Total kidney volume (TKV) and total liver volume (TLV) were quantified among secondary endpoints using MRI at baseline (BL) and end-of-treatment (EOT). Safety analyses focused on uric acid levels and hepatic/renal complications.

Results

The primary feasibility endpoint was reached for the WF (80%) but not the KD (43%) group. The lower percentage (KD) was driven by the pre-defined BHB threshold (≥0.8 mmol/l at all visits). 18/23 KD patients showed higher BHB levels at all on-diet visits compared to BL. Mean ΔhtTKV from BL to EOT was: Control +13.9ml/m±28.8, WF +7.1±47.2, KD -12.8±61.2; ANOVA vs. Control: p KD=0.08, WF=0.67. Mean ΔhtTLV from BL to EOT was: Control +42.2ml/m±166.0, WF -10.0±98.2, KD -55.1±72.5, with a statistically significant difference between KD and Control (p KD=0.01, WF=0.17). 2 patients experienced symptomatic kidney stones in KD. At EOT, uric acid levels > ULN were detected in 3 Control, 6 KD and 4 WF patients. Only 1 patient (Control) showed a mild ALT elevation (<1.5xULN). No cases of AST > ULN (EOT) or creatinine increase ≥50% from BL to EOT were recorded. eGFR increased in KD and WF (BL to EOT; KD 5.04ml/min±9.45, WF 0.21±5.12) while decreasing in the Control (-1.26±9.48). This difference was statistically significant comparing KD to Control (p KD=0.01, WF=0.5).

Conclusion

Both KDIs induced ketogenesis and were rated as feasible by patients, also when asked about long-term feasibility. KD did not reach the combined primary feasibility endpoint based on a predefined BHB threshold, but nearly all KD patients showed increased BHB at all visits. The impact of KD on TLV/TKV and eGFR is of special interest. Regarding safety, the formation of kidney stones will need specific attention.

Funding

• Other NIH Support