Abstract: TH-PO1225
Dapagliflozin Treatment Induces Alternate RAAS Activation in Stable Kidney Transplant Recipients
Session Information
- Late-Breaking Research Posters
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Shoumariyeh, Tarik, Medizinische Universitat Wien, Vienna, Austria
- Helk, Oliver, Medizinische Universitat Wien, Vienna, Austria
- Sridhar, Vikas, The University of British Columbia, Vancouver, British Columbia, Canada
- Kugathasan, Luxcia, University Health Network, Toronto, Ontario, Canada
- Domenig, Oliver, Attoquant Diagnostics GmbH, Vienna, Austria
- Cherney, David, University Health Network, Toronto, Ontario, Canada
- Kovarik, Johannes J., Medizinische Universitat Wien, Vienna, Austria
- Singh, Sunita K., University Health Network, Toronto, Ontario, Canada
- Kopecky, Chantal Maureen, University of New South Wales, Sydney, New South Wales, Australia
Background
Kidney transplant recipients (KTRs) remain at high risk for graft dysfunction and cardiovascular disease, yet the role of the renin–angiotensin–aldosterone system (RAAS) in these outcomes remains unclear. While sodium-glucose cotransporter 2 inhibitors (SGLT2i) offer kidney protection in chronic kidney disease (CKD), their effects on RAAS activity in KTRs are not well defined particularly in the context of renal denervation. We therefore evaluated the impact of dapagliflozin on RAAS profiles in stable KTRs.
Methods
We conducted an exploratory, secondary analysis of the INFINITI double-blind, randomized controlled trial (NCT04965935), which evaluated the efficacy and safety of 12 weeks of the SGLT2i dapagliflozin vs placebo in 52 stable KTR. Serum samples collected pre-treatment and 12 weeks post initiation were used for mass spectrometry–based RAAS profiling, including quantitative assessment of circulating angiotensin peptides and related metabolites. Statistical analysis was performed by applying a 3-way linear mixed-effects model.
This may be clearer, as post treatment may suggest 12 weeks after discontinuation of the drug.
Results
We detected a significant interaction (time x group) on the downstream product of alternate RAAS activation Ang 1-5: (b=3.29, 95%CI [0.87; 5.80], p=0.008) as well as on the RAAS activation marker Ang II: (b=48.44, 95%CI [2.37; 96.24], p=0.041), showing an increase over time for both peptides (Figure 1).
Conclusion
Dapagliflozin increased Ang 1–5 and Ang II 1-8 levels in stable KTRs . These findings suggest activation of the protective alternate RAAS axis and adaptation of the classical RAAS pathway, possibly due to increased natriuresis and effects on systemic volume. Our findings in the transplant setting are consistent with known effects of SGLT2i in native kidney physiology, offering additional mechanistic insights in this population.
Funding
- Government Support - Non-U.S.