Abstract 346: Mice Overexpressing Renin: a New Model of Progressive Chronic Kidney Disease

Background: Hypertension-induced chronic kidney disease in mouse models is quite fast and consequently away from the human pathology. There is an increasing need for a mouse model that can be used to delineate the pathogenic process leading to progressive renal disease. Aim: Our objective was dual: to investigate whether mice overexpressing renin ectopically at constant and high levels by genetic clamping (RenTg) could mimic kinetics and the physiopathological characteristics of hypertension-induced CKD and to identify cellular and/or molecular events characterizing the different steps of the progression of CKD. Results: We found that RenTg mice are hypertensive (123±7 vs to 90±2 mm Hg for the wt age-matched animals, p Conclusions: The RenTg strain develops progressively with age CKD. In this model, endothelial dysfunction is an early event preceding the structural and fibrotic alterations which ultimately lead to the development of CKD. This model can provide a useful tool allowing to gain new insights into the mechanisms of chronic renal failure and to identify new targets for arresting and/or reversing the development of CKD