BS24 Establishing a clinically relevant progressive model of ckd-associated cardiomyopathy in mice for insights into early-stage pathogenesis

Background Chronic kidney disease (CKD) affects 10–15% of the population globally. Reduced kidney function leads to CKD-associated cardiomyopathy characterised by increased left ventricular mass, diastolic and systolic dysfunction, and profound cardiac fibrosis. Despite high morbidity and mortality, CKD-associated cardiomyopathy remains poorly understood mechanistically. Current CKD animal models, like the 5/6 nephrectomy, primarily focus on late-stage CKD, hindering insights into early CKD-associated cardiomyopathy and progressive mechanistic actions. This limitation impedes the establishment of proactive therapeutic approaches. To address this gap, we propose characterizing a progressive murine model using an adenine-rich diet, allowing us to study the structural and functional differences between early and late-stage CKD-associated cardiomyopathy. Methods 8–9-week-old C57BL/6 male mice were fed either normal chow (n=9) or a 0.15% adenine rich diet (n=9), for up to 7 weeks. Blood levels of creatinine and urea were measured at 5 and 7 weeks to assess kidney dysfunction. Fibrosis was measured using western blotting and histology (via Martius Scarlet Blue staining). Heart, and kidney weight were recorded at the 5-week and 7-week endpoint, while body weight was measured weekly. Results Significant increases in both urea (pConclusion Adenine diet induced kidney disease model demonstrated progressive reduction of kidney function over 7 weeks, accompanied by cardiac fibrosis but without overt hypertrophy. Further studies will utilise this model to gain insights into the mechanisms driving CKD-associated cardiomyopathy pathogenesis. Conflict of Interest None