Key result
Enalapril and losartan significantly enhanced glomerular filtration rate and decreased albuminuria, mesangial expansion, renal fibrosis, and inflammation in mice with nephrotoxic nephritis.
Why the study?
Does inhibiting the renin-angiotensin-system with enalapril or losartan improve functional and morphological parameters in a murine model of nephrotoxic nephritis?
Does inhibiting the renin-angiotensin-system with enalapril or losartan improve functional and morphological parameters in a murine model of nephrotoxic nephritis?
Inhibiting the renin-angiotensin system with enalapril or losartan significantly improves functional and morphological parameters in a murine model of nephrotoxic nephritis.
NTN model may guide novel CKD therapies; leaves open clinical translation beyond ARB/ACEI.
INTRODUCTION: Chronic kidney disease (CKD) is a global health concern, but the current treatments only slow down the progression. Thus an improved understanding of the pathogenesis and novel treatments of CKD are needed. The nephrotoxic nephritis (NTN) model has the potential to study the pathogenesis of CKD as it resembles human CKD. The classical treatments with angiotensin II receptor blocker (ARB) or the angiotensin-converting enzyme inhibitor (ACE I) have shown a clinical effect in CKD. METHODS: We characterized the disease development in the NTN model over 11 weeks by investigating functional and histopathological changes. We tested doses of 15 and 30 mg/kg/day enalapril and losartan in the NTN model in order to investigate the effect of inhibiting the renin-angiotensin-system (RAS). RESULTS: The NTN model displayed albuminuria peaking on days 6-7, mesangial expansion (ME), renal fibrosis, inflammation and iron accumulation peaking on day 42. However, albuminuria, ME, renal fibrosis and inflammation were still significantly present on day 77, suggesting that the NTN model is useful for studying both the acute and chronic disease phases. Enalapril and losartan significantly enhanced the glomerular filtration rate (GFR) and decreased albuminuria, ME, renal fibrosis and inflammation of NTN-induced kidney disease in mice. CONCLUSIONS: This is the first study showing a comprehensive pathological description of the chronic features of the murine NTN model and that inhibiting the RAS pathway show a significant effect on functional and morphological parameters.
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Ougaard et al. (2018) studied Nephrotoxic nephritis (NTN) / Chronic kidney disease. Enalapril and losartan was evaluated on Glomerular filtration rate (GFR), albuminuria, mesangial expansion, renal fibrosis, and inflammation. Enalapril and losartan significantly enhanced glomerular filtration rate and decreased albuminuria, mesangial expansion, renal fibrosis, and inflammation in mice with nephrotoxic nephritis.
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