Abstract: TH-PO441
Metabolite Changes while Adhering to a Ketogenic Diet in Autosomal Dominant Polycystic Kidney Disease
Session Information
- Cystic Kidney Diseases: Clinical Assessment and Therapeutic Directions
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic
Authors
- Knol, Martine Geke Evelien, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
- Arjune, Sita, Exzellenzcluster CECAD in der Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
- van Gastel, Maatje D.A., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands
- Torres, Jacob A., University of California Santa Barbara, Santa Barbara, California, United States
- Weimbs, Thomas, University of California Santa Barbara, Santa Barbara, California, United States
- Mueller, Roman-Ulrich, Exzellenzcluster CECAD in der Universitat zu Koln, Koln, Nordrhein-Westfalen, Germany
- Rinschen, Markus M., Aarhus Universitet, Aarhus, Midtjylland, Denmark
Background
A dysregulated metabolism in Autosomal Dominant Polycystic Kidney Disease (ADPKD) contributes to cystogenesis. A ketogenic intervention, currently under investigation, profoundly changes metabolism and may offer protective effects in ADPKD. Various metabolites, including those from one-carbon metabolism, branched-chain amino acids, tryptophan, and glutamine, have been linked to altering disease progression in ADPKD. This study aimed to discover which metabolites change during ketogenic interventions using LC/MS/MS in the KETO-ADPKD trial.
Methods
Targeted metabolomics was performed using LC/MS/MS. Urine and serum samples from the KETO-ADPKD trial (n=63) were used. Participants followed a ketogenic diet (n=23), a 3-day water fast once monthly (n=21), or a control diet (n=19). Additionally, serum and kidney tissue were measured from Han:SPRD PKD rats (n=18) and WT rats (n=18) on a ketogenic or control diet.
Results
The average age was 41±9.6, and 44% were women. Of 21 participants, we had serum samples on baseline and 3 months after the ketogenic diet. 112 metabolites were quantified in the serum. Serum analysis revealed changes in 6 upregulated and 7 downregulated metabolites after a 3-month ketogenic diet. An increase in ketone bodies indicated adherence to a ketogenic diet. Further increases in citric acid and homocysteine, and decreases in hypotaurine, aspartate, and kynurenine were observed. In the spot urine, 89 metabolites were quantified and normalized to urinary creatinine. After 3 months, 9 metabolites were significantly more excreted, out of which 5 were aromatic amino acid metabolites (so-called uremic toxins), and 1 metabolite, tyrosine, was downregulated. We assessed the effect of the ketogenic diet in PKD rats and WT rats in kidney tissue and serum to compare to the human data, providing similar signatures.
Conclusion
Profound changes in ketosis-induced metabolism were observed. Of special interest are the decreased abundance of hypotaurine and kynurenine, which were found in both humans and animals. Elevated kynurenine levels, a uremic toxin, have been described before in ADPKD, and their relevance in cyst progression should be further studied. How hypotaurine is regulated in ADPKD and whether it plays a part in the pathophysiology still need to be unraveled.