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Liraglutide Improves the Kidney Function in a Murine Model of Chronic Kidney Disease
Maria E Ougaard1,2, Frederikke E Sembach3, Henrik E Jensen4
1Pathology & Imaging, Novo Nordisk, Måløv, Denmark, maria.e.ougaard@gmail.com.
Background:
Chronic kidney disease (CKD) is a global health burden, and the current treatment options only slow down the disease progression. GLP-1 receptor agonists (GLP-1 RA) have shown a renal protective effect in models of CKD; however, the mechanism behind the beneficial effect is not understood. In this study, we investigate the effect of the GLP-1 RA liraglutide in the nephrotoxic serum nephritis (NTN) CKD model. Moreover, we compare the gene expression pattern of liraglutide-treated mice to the gene expression pattern of mice treated with the angiotensin converting enzyme inhibitor, enalapril.
Methods:
The effect of liraglutide was tested in the NTN model by evaluating the glomerular filtration rate (GFR), albuminuria, mesangial expansion, renal fibrosis, and renal inflammation. Furthermore, the regulation of selected genes involved in CKD and in glomerular, cortical tubulointerstitial, and whole kidney structures was analyzed using a gene expression array on samples following laser capture microdissection.
Results:
Treatment with liraglutide improved CKD hallmarks including GFR, albuminuria, mesangial expansion, renal inflammation, and renal fibrosis. The gene expression revealed that both liraglutide and enalapril reversed the regulation of several fibrosis and inflammation associated genes, which are also regulated in human CKD patients. Furthermore, liraglutide and enalapril both regulated genes in the kidney involved in blood pressure control.
Conclusions:
Treatment with liraglutide improved the kidney function and diminished renal lesions in NTN-induced mice. Both liraglutide and enalapril reversed the regulation of genes involved in CKD and regulated genes involved in blood pressure control.
Insights
Glucagon-like peptide-1 receptor agonists (GLP-1 RA) like liraglutide show renal protection in chronic kidney disease (CKD) models. This study investigated liraglutide
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Chronic kidney disease (CKD) is a significant global health issue.
- Current treatments for CKD primarily slow disease progression.
- Glucagon-like peptide-1 receptor agonists (GLP-1 RA) exhibit potential renal protective effects, but mechanisms remain unclear.
Purpose of the Study:
- To investigate the renal protective effects of the GLP-1 RA liraglutide in a nephrotoxic serum nephritis (NTN) model of CKD.
- To compare the gene expression patterns induced by liraglutide with those of enalapril, an angiotensin-converting enzyme inhibitor.
Main Methods:
- Liraglutide's efficacy was assessed in the NTN mouse model by measuring glomerular filtration rate (GFR), albuminuria, mesangial expansion, renal fibrosis, and inflammation.
- Gene expression analysis was performed using laser capture microdissection and gene expression arrays to examine genes in kidney structures.
Main Results:
- Liraglutide treatment significantly improved key CKD indicators, including GFR, albuminuria, mesangial expansion, renal inflammation, and fibrosis.
- Both liraglutide and enalapril treatments reversed the dysregulation of genes associated with fibrosis and inflammation, mirroring patterns seen in human CKD.
- Both drugs modulated genes involved in blood pressure regulation within the kidney.
Conclusions:
- Liraglutide demonstrates significant renoprotective effects, improving kidney function and reducing renal lesions in an NTN-induced mouse model.
- Both liraglutide and enalapril effectively reversed the gene expression changes associated with CKD and influenced genes related to blood pressure control.
