Abstract: SA-PO0268
Urine Exosomal miRNA Alterations Induced by Vicadrostat and Empagliflozin in Patients with CKD
Session Information
- Pharmacology
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Delic, Denis, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
- Gashaw, Isabella A, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany
- Duran-Fernandez, Ileana, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
- Cronin, Lisa, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, United States
- Hauske, Sibylle Jenny, Boehringer Ingelheim International GmbH, Ingelheim, Germany
- Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Tuttle, Katherine R., Providence Inland Northwest Health, Spokane, Washington, United States
Background
Vicadrostat (VICA), a selective aldosterone synthase inhibitor, dose-dependently reduced albuminuria with concurrent renin–angiotensin system inhibition and empagliflozin (EMPA), suggesting an additive efficacy for chronic kidney disease (CKD) treatment. Specific urinary exosomal microRNAs (miRNAs) may reflect key processes involved in CKD progression. We aimed to mechanistically differentiate the effects on urinary extracellular vesicle (uEV) miRNA expression in participants treated with VICA alone or VICA+EMPA (VicaEmpa).
Methods
Small RNA sequencing was conducted on urinary exosomal miRNAs from 437 participants with CKD (with/without diabetes) who completed the phase II trial of VICA with/without EMPA (NCT05182840). For differentially expressed urinary exosomal miRNAs (fold change: 1.5; P≤0.01 end of treatment vs baseline) participants with ≥30% UACR reduction (responders) treated with 10 mg or 20 mg VICA were pooled and compared with/without EMPA. Correlations with change in UACR were assessed.
Results
Responders treated with 10 mg or 20 mg VICA monotherapy had increased uEV miRNA expression of 7 miRNAs and a decreased expression of 2 miRNAs. Responders treated with 10 mg or 20 mg VicaEmpa had a decreased expression of 26 miRNAs. Changes in miRNA-142-5p correlated significantly with changes in UACR in participants treated with VICA alone whereas changes in expression of 8 uEV miRNAs correlated with UACR in those treated with VicaEmpa (Table). No changes in the identified uEV miRNAs were apparent in non-responding or placebo-treated participants. Baseline UACR, eGFR or aldosterone level were not associated with changes in miRNAs. An in vitro, kidney cell-specific uEV miRNA expression database showed that differentially regulated miRNAs are expressed in various kidney cell types.
Conclusion
VicaEmpa or VICA alone altered various uEV miRNAs involved in immunomodulatory and fibrotic pathways irrespective of diabetes status. Regulation of miRNAs in the kidney provides insights into mechanisms of action for VICA in CKD.
Funding
- Commercial Support – Boehringer Ingelheim