Abstract: TH-PO1207
Urinary Proteomic Changes Associated with a Healthier Kidney Phenotype After Dapagliflozin Therapy in Adolescent Patients with Type 1 Diabetes
Session Information
- Late-Breaking Research Posters
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 702 Diabetic Kidney Disease: Clinical
Authors
- Hampson, Hailey E, University of Washington School of Medicine, Seattle, Washington, United States
- Tommerdahl, Kalie L., University of Washington School of Medicine, Seattle, Washington, United States
- Mahmud, Farid H., The Hospital for Sick Children Department of Paediatrics, Toronto, Ontario, Canada
- Karihaloo, Anil K., Novo Nordisk Fonden, Hellerup, Capital Region of Denmark, Denmark
- Clarke, Antoine, The Hospital for Sick Children Department of Paediatrics, Toronto, Ontario, Canada
- Choi, Ye Ji, University of Washington School of Medicine, Seattle, Washington, United States
- Cherney, David, University Health Network, Toronto, Ontario, Canada
- Heerspink, Hiddo Jan L., Universiteit Groningen Faculteit Medische Wetenschappen, Groningen, GR, Netherlands
- Narongkiatikhun, Phoom, Chiang Mai University Faculty of Medicine, Chiang Mai, Thailand
- Clarson, Cheril L, London Health Sciences Centre, London, Ontario, Canada
- Bjornstad, Petter, University of Washington School of Medicine, Seattle, Washington, United States
- Pyle, Laura, University of Washington School of Medicine, Seattle, Washington, United States
Background
In youth, sodium-glucose co-transporter 2 inhibitors (SGLT2i) demonstrate cardio-kidney-metabolic protection through attenuation of hyperglycemia and hyperfiltration. We investigated the effect of dapagliflozin on the plasma and urine proteome in youth with type 1 diabetes (T1D).
Methods
Proteins were quantified using the SomaScan platform (plasma: 11k panel, urine: 7k panel) before and after 16 weeks of dapagliflozin 5 mg daily or placebo in youth with T1D from the randomized-controlled trial, Adolescent T1D Treatment with SGLT2i for hyperglycEMia & hyperfiltration Trial (ATTEMPT). SomaScan relative fluorescence units were log2 transformed post normalization. Linear mixed models were fit for each protein with treatment, visit, and their interaction as fixed effects, and a random intercept for participant. Multiple testing was controlled at false discovery rate (FDR) <0.05.
Results
Participants (N=97) were 16.0±2.3 years, 47% male, with T1D duration 7.3±4.2 years, HbA1c 7.7±0.8%, and BMI 25.0±5.7 kg/m2. Mixed effects analyses of urinary proteins found 12 proteins involved in energy metabolism or epithelial repair that increased with dapagliflozin vs. placebo, while 74 proteins associated with tubular injury, fibrosis, and inflammation decreased. Urinary epidermal growth factor (EGF, a kidney protective factor) increased, while growth differentiation factor 15 (GDF15, a tubular stress marker) fell markedly. Pro-fibrotic and injury-associated markers, including tissue inhibitor of metalloproteinases-2 (TIMP2), matrix metalloproteinase-7 (MMP7), and insulin-like growth factor binding protein 2/5 (IGFBP2/5), were significantly reduced in urine with dapagliflozin.
Conclusion
Dapagliflozin therapy in youth with T1D favorably shifted urinary protein signatures toward reduced tubular injury and fibrosis, while enhancing urinary markers of epithelial repair and kidney protection, underscoring the kidney-specific effects of SGLT2i. These findings provide molecular evidence supporting the kidney protective potential of SGLT2 inhibition in youth with T1D and highlight urinary proteomics as a sensitive tool for detecting early kidney-specific therapeutic effects.
Funding
- Private Foundation Support