Kidney Week

Abstract: TH-PO0342

Cardio-Kidney Effects of Dapagliflozin in Patients at Elevated Cardiovascular Risk with or Without Type 2 Diabetes

Session Information

• Hypertension and CVD: Clinical - 1
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1602 Hypertension and CVD: Clinical

Authors

• Sridhar, Vikas, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada

Vikas Sridhar, MD

• Kugathasan, Luxcia, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada

Luxcia Kugathasan

• Lytvyn, Yuliya, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada

Yuliya Lytvyn, PhD

• Deng, Yangqing, University Health Network, Toronto, Ontario, Canada

Yangqing Deng, PhD

• Liu, Hongyan, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada

Hongyan Liu

• Lovblom, Leif Erik, University Health Network, Toronto, Ontario, Canada

Leif Erik Lovblom, PhD

• Tse, Josephine, University Health Network, Toronto, Ontario, Canada

Josephine Tse, RN

• Nardone, Massimo, University Health Network, Toronto, Ontario, Canada

Massimo Nardone, PhD

• Floras, John, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada

John Floras, MD, PhD

• Stevens, Jasper, Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands

Jasper Stevens, PhD

• Touw, Daniel J., Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands

Daniel J. Touw, PharmD, PhD

• Burger, Dylan, University of Ottawa, Ottawa, Ontario, Canada

Dylan Burger, PhD

• Heerspink, Hiddo Jan L., Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands

Hiddo Jan L. Heerspink, PhD

• Lovshin, Julie A., University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada

Julie A. Lovshin, MD, PhD

• Perkins, Bruce A., University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada

Bruce A. Perkins, MD, MPH

• Cherney, David, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada

David Cherney, MD, PhD

Background

We investigated the physiological effects of 12 weeks of sodium-glucose cotransporter 2 inhibition (dapagliflozin 10mg daily) on cardiac, vascular, kidney, & neurohormonal pathways in participants at elevated cardiovascular (CV) risk.

Methods

This randomized double-blind, parallel-group, placebo-controlled study enrolled 51 participants & comprised three sequential physiologic assessments under clamped euglycemia (4 to 6 mmol/l): baseline, at 1 week & 12 weeks of treatment. The primary outcome measured vascular arterial stiffness, captured by pulse wave velocity & augmentation indices. Secondary outcomes included: blood pressure (BP), body fluid composition, non-invasive cardiac output monitoring, arterial vasodilatation tests, heart rate variability, echocardiography, iohexol-measured glomerular filtration rate (GFR) & natriuresis.

Results

Dapagliflozin decreased vascular arterial stiffness, as measured by aortic augmentation index (–7.38±2.84%, p=0.01), after 12 weeks. Dapagliflozin acutely decreased supine measures of systolic BP (9.38±3.84 mmHg) & extracellular fluid (–0.84±0.27 L), with sustained reductions in thoracic fluid content at 12 weeks (–3.25±1.47 1/kΩ). There was evidence of tubuloglomerular feedback activation with reductions in measured GFR (–5.82±2.11 ml/min/1.73m²), acute increases in proximal sodium excretion (5.10±2.22%) & absolute fractional distal sodium reabsorption (4.41±2.05%), & increases in urine adenosine.

Conclusion

Dapagliflozin induced multiple mechanisms associated with CV & kidney protection in patients at varying levels of CV risk in whom evidence of clinical protection is lacking.

Funding

• Commercial Support – AstraZeneca

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025mkxzx6mr