Kidney Week

Abstract: FR-PO0069

The Urinary Proteome as a Predictor of Treatment Response to Tolvaptan in ADPKD

Session Information

• ADPKD and Cystic Kidney Disease - 2
  October 23, 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

• Garmaa, Gantsetseg, Universitatsklinikum Koln, Cologne, NRW, Germany

Gantsetseg Garmaa, MD, PhD

• Aydogan Balaban, Hande Özge, Universitatsklinikum Koln, Cologne, NRW, Germany

Hande Özge Aydogan Balaban, MSc

• Antczak, Philipp, Universitatsklinikum Koln, Cologne, NRW, Germany

Philipp Antczak, PhD

• Mueller, Roman-Ulrich, Universitatsklinikum Koln, Cologne, NRW, Germany

Roman-Ulrich Mueller, MD

Background

Tolvaptan is the only approved targeted treatment for ADPKD and acts by blocking the V₂R. Currently, it is not possible to predict individual patients' treatment response. We aimed to identify a proteomic signature associated with tolvaptan treatment and the clinical response to tolvaptan, as reflected in the ΔeGFR slope (Δ = on – before tolvaptan).

Methods

We analyzed longitudinal urinary proteomic profiles from the German AD(H)PKD cohort. Two linear mixed-effects models, adjusted for age, sex, and repeated measures, were used. Paired treatment model: A within-patient analysis of 35 patients (n=105 samples) comparing “before” and “on” tolvaptan data to identify drug-induced proteomic changes. Continuous response model: An association analysis of 63 patients (n=136 samples) using “on” tolvaptan data to identify proteins correlated with ΔeGFR slope, representing clinical response. Functional enrichment was performed using KEGG GSEA.

Results

In the paired analysis, tolvaptan significantly altered four proteins (FDR<0.05): histidine-rich glycoprotein (HRG) and vitamin D-binding protein (GC), and cholesteryl ester transfer protein (CETP) decreased, while dihydrolipoamide succinyl transferase (DLST) increased. Pathway analysis indicated strong enrichment of the Complement and coagulation cascades, and Neutrophil extracellular trap formation among proteins linked to treatment, along with cAMP signaling, consistent with V₂R blockade and reduced AQP2 during treatment (n=31 patients, median ΔAQP2: -0.55). In the response model, no individual proteins reached FDR significance. But pathway analysis showed that the Complement and coagulation cascades correlated with a more negative ΔeGFR slope, whereas a positive ΔeGFR slope was associated with enrichment of Metabolic pathways, such as Carbohydrate metabolism and Glycolysis/Gluconeogenesis.

Conclusion

Tolvaptan induces a urinary proteomic signature in ADPKD, with pathway alterations consistent with V₂R blockade and downstream remodeling of immune-hemostatic, complement, and metabolic pathways. The observed changes in HRG, GC, CETP, and DLST may reflect remodeling of tubular injury, immune-hemostatic activity, altered lipid and mitochondrial metabolic pathways. In conclusion, these findings indicate the power of urinary proteomics to delineate the biological effects of pharmacological therapies in ADPKD and its potential to predict personalized treatment responses.

Funding

• Government Support – Non-U.S.