Abstract: SA-PO0318
Thyroid Hormone Nanotherapy Improves Kidney Function and Structure in Diabetic Nephropathy
Session Information
- Diabetic Kidney Disease: Basic and Translational Science Advances - 2
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Lavecchia, Angelo Michele, IRCCS Istituto di Ricerche Farmacologiche Mario Negri Centro Anna Maria Astori, Bergamo, Lombardy, Italy
- Mourouzis, Iordanis, Ethniko kai Kapodistriako Panepistemio Athenon Iatrike Schole, Athens, Attica, Greece
- Skourtis, Dimitris, Ethniko kai Kapodistriako Panepistemio Athenon, Athens, Attica, Greece
- Katsaouni, Athanasia-Paraskevi, Ethniko kai Kapodistriako Panepistemio Athenon Iatrike Schole, Athens, Attica, Greece
- Cerullo, Domenico, IRCCS Istituto di Ricerche Farmacologiche Mario Negri Centro Anna Maria Astori, Bergamo, Lombardy, Italy
- Iatrou, Hermis, Ethniko kai Kapodistriako Panepistemio Athenon Iatrike Schole, Athens, Attica, Greece
- Remuzzi, Giuseppe, IRCCS Istituto di Ricerche Farmacologiche Mario Negri Centro Anna Maria Astori, Bergamo, Lombardy, Italy
- Xinaris, Christodoulos, IRCCS Istituto di Ricerche Farmacologiche Mario Negri Centro Anna Maria Astori, Bergamo, Lombardy, Italy
Background
Diabetic nephropathy (DN) is one of major diabetes’ complications, developing in approximately 40% of diabetic patients, one third of whom progress to end stage renal disease. Standard treatments provide only partial reno-protection, leaving the development of therapies for DN an unmet clinical need. The diabetic milieu induced structural, metabolic and functional kidney remodeling, that often led to DN. Our studies indicates that diabetes-induced podocytes alterations are manifestations of a maladaptive recapitulation of early developmental steps, which are controlled by the thyroid hormone (TH)/TH receptor axis. Although TH treatment improves renal function in patients with chronic kidney disease, translating this strategy into clinical practice is not without problems.
Methods
To maximize the regenerative capacities of TH, reducing its possible adverse effects, we have developed an innovative nanoparticles(NPs)-based delivery system (NanoT3) that targets and delivers TH mainly in diabetes-injured podocytes. Following in vitro and in vivo characterization of its toxicity and targeting specificity, the therapeutic efficacy of NanoT3 was tested in Zucker diabetic fatty (ZDF) rats. NanoT3 was administered intraperitoneally for 3 months, at doses corresponding to 6 μg/Kg T3 once every 5 days. Another group of ZDF rats was treated with empty NPs (vehicle).
Results
At the end of the study, NanoT3-treated ZDF rats showed a significant reduction in urine protein to creatinine ratio (UPCR) compared to vehicle-treated animals. The reduction in UPCR was accompanied by a decrease in glomerular filtration rate, indicating the selectivity of our system, since hyperfiltration is a well-known side-effect of systemic TH administration. Consistently, treatments with NanoT3 strongly reduced glomerulosclerosis, tubular dilation and atrophy in ZDF rats. Finally, scanning electron microscopy showed that, in contrast to diabetic animals treated with vehicle, NanoT3-treated ZDF rats displayed good preservation of the podocyte cytoarchitecture and reduced effacement of the interdigitating foot processes.
Conclusion
In conclusion our study indicated that NanoT3 administration could be a safe and efficient strategy to improve structure and function in diabetes-injured kidney.