Introduction Chronic kidney disease (CKD) affects 10–15% of the global population. CKD causes systemic inflammation (marked by elevated levels of C-reactive protein, interleukins and tumour necrosis factor-alpha) and CKD-associated cardiomyopathy characterised by increased left ventricular mass, diastolic and systolic dysfunction, profound cardiac fibrosis and atrial and ventricular arrhythmias. The mechanistic links between CKD induced systemic inflammation and cardiac remodelling are unclear, especially in early CKD stages. Therefore, we propose characterizing a CKD mouse model using an adenine-rich diet to compare structural and functional changes in CKD-related cardiomyopathy between early and late stages, and the link to inflammation and other systemic consequences of CKD. Methods 8–9-week-old C57BL/6 female and male mice were fed a normal chow or 0.15% adenine rich diet, for up to 7-weeks. Following the diet, blood levels of creatinine and urea were measured to assess kidney dysfunction. Inflammatory markers were sent to be analysed through an o-link panel, and urea and creatinine were analysed through IDEXX. Hearts were isolated for ex vivo cardiac electrophysiological testing and stored for future imaging. Results Significant and progressive increase in urea (5-week, p = 0.0053 and 7-week, p p = 0.0017 and 7-week, p p Conclusion The adenine-rich diet induced progressive CKD in this mouse model, which is associated with significant systemic inflammation and early cardiac remodelling characterised by increased fibrosis. Ongoing investigations into electrophysiological changes aim to further elucidate the mechanistic link between CKD-induced inflammation and cardiac dysfunction.
Tompkins et al. (Wed,) studied this question.