Modelling chronic kidney disease-induced cardiovascular calcifications in rats using an adenine/phosphate-enriched diet

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Blot, Gérémy | Louvet, Loïc | de Berny, Quentin | Boudot, Cédric | Spicher, Pierre | Issa, Nervana | Kamel, Said | Hénaut, Lucie | Bennis, Youssef

Edité par CCSD ; Elsevier ; Société française de cardiologie [2008-....] -

International audience. IntroductionIn patients with chronic kidney disease (CKD), cardiovascular calcifications, including aortic valve calcification, are more frequent, appear earlier and progress more quickly, leading to a mortality rate three times higher than in the general population. To date, modelling these complications is challenging but required to test innovative therapeutic strategies.ObjectiveThis work aims to establish a rat model of progressive CKD associated with the development of aortic and valvular calcifications, using a diet enriched with adenine and phosphate.MethodTwenty-four male Sprague Dawley rats aged 8 weeks were divided into two groups: a control group fed a standard diet (CT, n = 12) and a group fed a diet enriched with 0.3% adenine and 1.2% phosphate (AP, n = 12), over a period of 9 weeks. Their blood was collected for hematological and biochemical analyses at euthanasia. The kidneys, heart, aorta and aortic valve of each animal were collected for biochemical and histological analyses. Cardiovascular calcifications were monitored by alizarin red and osteosense stainings, and calcium content assay.ResultsRats fed an AP diet gained less weight than control rats over 9 weeks. AP diet did not induce mortality. AP rats showed a ten-fold increase in serum urea and creatinine concentrations compared to CT rats. These effects were associated with anemia, uremic toxins accumulation and an increase in the phosphocalcic product. The kidneys of AP rats were smaller and showed granular appearance, and the weight of their left ventricle was significantly lower compared to CT rats. The calcium content was significantly higher in aorta and aortic valve of AP compared to CT rats and associated with large areas of calcification deposits.ConclusionThe proposed model allows the development of a severe CKD associated with both aortic and aortic valve calcifications within 9 weeks. Functional consequences are currently studied by echocardiography and magnetic resonance imaging.

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