Abstract: FR-OR68
Semaglutide Improves Kidney Function and Inflammatory Status in a Mouse Model of Glomerulonephritis
Session Information
- Innovative AKI Strategies and Drug Discoveries
October 25, 2024 | Location: Room 7, Convention Center
Abstract Time: 05:10 PM - 05:20 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Rakipovski, Günaj, Novo Nordisk A/S, Bagsvaerd, Hovedstaden, Denmark
- Ougaard, Maria Katarina, Gubra A/S, Horsholm, Denmark
- Belmar, Nicolas, Novo Nordisk A/S, Bagsvaerd, Hovedstaden, Denmark
- Østergaard, Mette Viberg, Novo Nordisk A/S, Bagsvaerd, Hovedstaden, Denmark
- Endlich, Nicole, NIPOKA, Greifswald, Germany
- Rolin, Bidda, Novo Nordisk A/S, Bagsvaerd, Hovedstaden, Denmark
Background
Semaglutide, a GLP-1 receptor agonist, used for weight management and treatment of type 2 diabetes has recently shown a reduction in kidney disease progression and mortality in the FLOW trial. In this study, we used a mouse model of glomerulonephritis known as nephrotoxic serum nephritis (NTN) to evaluate the effects of semaglutide on kidney function, inflammation and morphology
Methods
Glomerulonephritis was induced in female CD1 mice (8-10 weeks old) by intravenous injection of 100 µl nephrotoxic serum (NTS) and allocated to 4 groups: semaglutide (n=12), enalapril (n=10), NTN control (n=12) and healthy control (n=10). Active compound or vehicle was administrated once daily for 14 days.Urine samples were collected in metabolic cages and urinary albumin, creatinine and neutrophil gelatinase-associated lipocalin (NGAL) excretion were measured. The glomerular filtration rate (GFR) was measured on day 12 by transcutaneous method. At termination, the kidneys were collected and processed for histopathological analyses. Renal inflammation was evaluated by staining for CD45 by immunohistochemistry and mesangial expansion was measured as a mean score of PAS stained kidney sections. The podocyte foot process morphology was assessed by measuring the filtration slit density (FSD) by staining for nephrin.
Results
Treatment with semaglutide significantly increased GFR on day 12, and significantly reduced uACR and NGAL on days 7-8 compared to the vehicle treatment. The CD45 staining was significantly reduced in kidneys from mice receiving semaglutide, indicating a reduction in inflammation. Evaluation of mesangial expansion showed that treatment with semaglutide significantly reduced renal lesions compared to the vehicle group. Finally, semaglutide significantly improved FSD. Enalapril showed the expected efficacy by improving urinary markers of kidney function and histopathology.
Conclusion
Semaglutide improved the kidney function in the NTN mice by significantly increasing GFR and lowering uACR and NGAL.
Furthermore, semaglutide significantly reduced renal inflammation and measangial expansion and improved renal filtration barrier function in the NTN mice. These data support the notion that semaglutide has anti-inflammatory properties beyond the well known diabetes and weight management properties.
Funding
- Commercial Support – Novo Nordisk A/S