Semaglutide Protects Kidneys from Damage in a Non-Diabetic Mouse Model

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) like Semaglutide are well-known for their efficacy in managing type 2 diabetes and obesity, often showing beneficial effects on cardiovascular and renal health in diabetic patients. However, the precise molecular mechanisms by which GLP-1 RAs exert their renoprotective effects in non-diabetic kidney injury models, such as nephrotoxic serum nephritis (NSN), remain largely unexplored. This study aimed to characterize these mechanisms, specifically addressing how Semaglutide impacts kidney pathology and molecular pathways in a non-diabetic acute kidney injury setting.

Treatment with Semaglutide significantly attenuated kidney injury in the NSN model. Compared to the vehicle-treated NSN group, Semaglutide-treated mice showed a remarkable 58% reduction in albuminuria (a key marker of kidney damage) by week 4 (p<0.001), alongside a 32% decrease in serum creatinine levels (p<0.01). Histopathological examination revealed significantly less glomerular damage and tubular injury in the treated group. > The most striking finding was a 75% decrease in the expression of pro-inflammatory cytokines such as TNF-α and IL-6 in kidney tissue (p<0.001), indicating potent anti-inflammatory effects. Furthermore, Semaglutide treatment led to a 45% reduction in renal fibrosis markers, including collagen I and α-SMA expression (p<0.05), and a 2.3-fold increase in antioxidant enzyme activity, suggesting a multi-faceted protective mechanism. These improvements were accompanied by a 25% preservation of podocyte integrity, crucial for kidney filtration.