Abstract: FR-PO0537
Tumor Necrosis Factor Receptor Signaling in Response to SGLT2 Inhibition in Kidney Transplant Recipients: An Analysis of the INFINITI Trial
Session Information
- CKM: Clinical - Trials, Epidemiology, and Biomarkers
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 602 Cardiovascular-Kidney-Metabolic Health: Clinical
Authors
- Sridhar, Vikas, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
- Kugathasan, Luxcia, University Health Network, Toronto, Ontario, Canada
- Cherney, David, University Health Network, Toronto, Ontario, Canada
- Singh, Sunita K., University Health Network, Toronto, Ontario, Canada
Background
Tumor necrosis factor receptor (TNFR) signaling is a robust marker of inflammatory activation and is associated with kidney disease progression. Its role in modulating response to sodium-glucose cotransporter-2 (SGLT2) inhibition in kidney transplant recipients (KTR) remains unknown.
Methods
We conducted a biomarker analysis of the INFINITI trial evaluating dapagliflozin versus placebo in 50 stable KTR over 12 weeks. Plasma TNFRI and TNFRII were measured at baseline and follow-up. Principal component analysis (PCA) was used to evaluate combined changes in TNFR biomarkers. Linear mixed-effects models assessed associations between TNFR and renal tubular response markers, including fractional excretion of sodium, 24-hour urinary glucose excretion, and measured glomerular filtration rate. Additional analyses examined associations between baseline TNFR levels and blood pressure outcomes.
Results
Dapagliflozin significantly reduced TNFRII levels compared with placebo (−1337 pg/mL; 95% CI – 2469 to –204; 1A). PCA of TNFRI and TNFRII demonstrated an overall shift toward lower TNFR signaling with dapagliflozin (p=0.02; 1B). Participants with higher baseline TNFRII levels reported increased fractional excretion of sodium with dapagliflozin compared with those with lower baseline TNFRII levels (p interaction
=0.01) and greater reductions in blood pressure, including seated systolic blood pressure (p=0.01), supine diastolic blood pressure (p=0.02) and supine mean arterial pressure (p=0.01). In addition, greater reductions in TNFRI with dapagliflozin were associated with stronger treatment responses, including increased urinary glucose excretion and greater reductions in measured GFR (p=0.04 both; 1C–D).
Conclusion
In stable KTR, SGLT2 inhibition with dapagliflozin reduces circulating TNFR. TNFR signaling is associated with distinct renal, tubular and hemodynamic responses, suggesting it may identify biologically distinct responders to SGLT2 inhibition in this population.
Funding
- Commercial Support – AstraZeneca