Kidney Week

Abstract: SA-PO0107

Proteome of Small Urinary Extracellular Vesicles Reflects Ketogenic Dietary Interventions in ADPKD

Session Information

• ADPKD and Cystic Kidney Disease - 3
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)

Authors

• Droste, Marvin, Universitatsklinikum Koln Klinik II fur Innere Medizin Nephrologie Rheumatologie Diabetologie und Allgemeine Innere Medizin, Cologne, NRW, Germany

Marvin Droste, MD

• Lin, Sophie, Universitatsklinikum Koln Klinik II fur Innere Medizin Nephrologie Rheumatologie Diabetologie und Allgemeine Innere Medizin, Cologne, NRW, Germany

Sophie Lin

• Garmaa, Gantsetseg, Universitatsklinikum Koln Klinik II fur Innere Medizin Nephrologie Rheumatologie Diabetologie und Allgemeine Innere Medizin, Cologne, NRW, Germany

Gantsetseg Garmaa, MD, PhD

• Lackmann, Jan-Wilm, Exzellenzcluster CECAD in der Universitat zu Koln, Cologne, NRW, Germany

Jan-Wilm Lackmann, PhD

• Cukoski, Sadrija, Universitatsklinikum Koln Klinik II fur Innere Medizin Nephrologie Rheumatologie Diabetologie und Allgemeine Innere Medizin, Cologne, NRW, Germany

Sadrija Cukoski

• Antczak, Philipp, Universitatsklinikum Koln Klinik II fur Innere Medizin Nephrologie Rheumatologie Diabetologie und Allgemeine Innere Medizin, Cologne, NRW, Germany

Philipp Antczak, PhD

• Mueller, Roman-Ulrich, Universitatsklinikum Koln Klinik II fur Innere Medizin Nephrologie Rheumatologie Diabetologie und Allgemeine Innere Medizin, Cologne, NRW, Germany

Roman-Ulrich Mueller, MD

Background

Dietary interventions are increasingly studied in kidney diseases, including ADPKD. In animal models, ketogenic diets attenuated cyst growth and slowed down GFR loss. The KETO-ADPKD trial was the first proof-of-concept study that recapitulated these findings in human subjects, yet the underlying molecular mechanisms are not fully elucidated and thus mainly extrapolated from animal studies. Here we characterized the proteome of small urinary extracellular vesicles (uEVs) to identify key signaling pathways involved in renal tissue responses to ketogenic diet in ADPKD patients.

Methods

Urine samples (n = 40) and corresponding clinical data were retrieved from the KETO-ADPKD trial (ketogenic diet group = KD, water fasting group = WF, control group = Ctrl). uEVs were enriched by differential ultracentrifugation and characterized according to the MISEV guidelines. uEV proteins were digested and analyzed by LC-MS/MS. Linear mixed effects models were applied to analyze alterations of protein abundance from baseline to end of treatment and complemented by GO term and KEGG pathway enrichment.

Results

Protein rank analysis confirmed representation of EV and nephron segment markers. Enrichment analyses revealed a strong metabolic signature reflecting adaptation to glucose deprivation. Moreover, proteins associated with aberrant cell death involved in fibrosis (such as necroptosis and efferocytosis) were downregulated in the KD and WF groups. In the KD group, proteins related to NK cell mediated cytotoxicity and mTOR signaling were also downregulated. Overall, substantially more proteins were significantly regulated in the KD vs. the WF group. Interestingly, ANTXR1 and CLEC3B, which are both associated with extracellular matrix turnover, were among the five most differentially regulated proteins in the KD group.

Conclusion

The proteomic landscape of uEVs reflects the metabolic adaptation to ketogenic diets in ADPKD patients and points towards an interplay between these adaptive processes and extracellular matrix remodeling. The therapeutic effect therefore appears to extend beyond the reduced survival of cyst-forming epithelia. Although starvation is traditionally thought to promote fibrosis, in ADPKD, restoring the aberrantly glycolysis-dependent proliferative signaling through glucose deprivation may be protective. Further research is warranted to confirm this hypothesis.

Acknowledgment

The KETO-ADPKD trial was funded by the PKD Foundation. Additional support was provided by the Medical Faculty of the University of Cologne through the Köln Fortune Program (to M.D. and S.L.) and the Cologne Clinician Scientist Program (to S.C.), the Else Kröner Fresenius-Stiftung and Eva Luise & Horst Köhler Stiftung through the Research Center on Rare Kidney Diseases (RECORD; to M.D.), and the Jörg Bernards Stiftung and the German Research Foundation/TRR422 (to P.A.).

Funding

• Private Foundation Support