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 aim to characterize 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 cardiac electrophysiological alterations and other systemic consequences from 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. Optical mapping was conducted to assess the cardiac electrical activity, comparing adenine-fed mice to control.

Results.

Significant and progressive increase in urea (5-week, p = 0.0053 and 7-week, p <0.0001) and creatinine (5-week, p = 0.0017 and 7-week, p <0.0001) levels were observed between control and adenine-fed mice, reflecting kidney dysfunction, see figure 1. Optical mapping analysis identified adenine-induced CKD  prolongs action potential duration, as seen in figure 2.

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. Furthermore, adenine-diet induces electrophysiological alterations by prolonging action potential duration.