Kidney Week

Abstract: TH-PO0834

Long-Term Treatment with an ACE Inhibitor and an SGLT2 Inhibitor Causes Concentric Hypertrophy of Glomerular Arterioles

Session Information

• Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

• 1900 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

• Weissbach, Hannah, Universitatsklinikum Carl Gustav Carus, Dresden, SN, Germany

Hannah Weissbach, MS

• Seitz, Meike, Universitatsklinikum Carl Gustav Carus, Dresden, SN, Germany

Meike Seitz, MS, MSc

• Sradnick, Jan, Universitatsklinikum Carl Gustav Carus, Dresden, SN, Germany

Jan Sradnick, PhD

• Pieper, Michael P., Boehringer Ingelheim International GmbH, Ingelheim am Rhein, RP, Germany

Michael P. Pieper, DVM

• Steglich, Anne, Universitatsklinikum Carl Gustav Carus, Dresden, SN, Germany

Anne Steglich

• Todorov, Vladimir T., Universitatsklinikum Carl Gustav Carus, Dresden, SN, Germany

Vladimir T. Todorov, MD, PhD

• Hugo, Christian, Universitatsklinikum Carl Gustav Carus, Dresden, SN, Germany

Christian Hugo, MD

Background

Inhibitors of the renin-angiotensin system (RAS) and the sodium-glucose transporter 2 (SGLT2) are commonly used in the treatment of progressive kidney disease with and without hypertension. Chronic RAS stimulation by ACE inhibition (ACEi) or renin deficiency has been associated with concentric thickening of glomerular arterioles. However, the effects of combined ACEi/SGLT2i on renin cell dynamics and vascular remodeling remain incompletely understood. In this study, we examine chronic renin cell stimulation under combined ACEi/SGLT2i.

Methods

Male mRen-rtTAm2-LC1-tdT mice (n= 6-9) were treated with doxycycline to induce tdTomato (tdT) reporter protein expression in renin cells. After a 2-week washout period, treatment with either enalapril, empagliflozin, or both in combination started for 3 months. Kidney biopsies were collected, analyzed by fluorescence stainings to quantify tdT- and renin-positive cell number and to measure arteriole thickness. Single Cell Sequencing of tdT-positive cells was performed.

Results

Enalapril treatment significantly increased afferent arteriole wall thickness by 22% compared with placebo, whereas combined ACEi/SGLT2i therapy induced a significantly more pronounced increase of 51% compared to placebo and enalapril alone, indicating a synergistic effect. Luminal diameter was significantly reduced by 34% with enalapril and by 27% with combination therapy. The number of tdT-positive cells increased 1.4-fold and renin-positive cells increased 1.8-fold following enalapril treatment. This increase was significantly greater after combined ACEi/SGLT2i treatment, with tdT-positive cells increasing 3.6-fold and renin-positive cells increasing 4.5-fold. Single-cell RNA sequencing revealed distinct gene expression profiles in tdT-positive cells from combination-treated mice compared to each monotherapy.

Conclusion

Long-term inhibition of ACEi and SGLT2i promotes concentric hypertrophy of the afferent arteriole, accompanied by expansion and phenotypic modulation of renin-lineage cells. Notably, combined ACEi/SGLT2i results in a more pronounced vascular remodeling than ACEi alone, suggesting synergistic effects on renin cell plasticity and arteriolar structure. These findings highlight previously unrecognized consequences of combination therapy and warrant further investigation into their functional and clinical implications.

Funding

• Government Support – Non-U.S.