BS11 Optimising the adenine-induced rat model of chronic kidney disease to investigate the mechanism of cardiorenal disease

Introduction Myocardial ischaemia-reperfusion injury (IRI) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD). The dietary adenine model of CKD is one of the most representative models of human CKD. However, most studies administer adenine throughout the entire study, which risks potential direct cardiotoxic effects of adenine. Therefore, we aimed to modify this model to address if the CKD-associated cardiovascular dysfunction persists following the withdrawal of adenine. Methods Male Wistar rats, aged 8–9 weeks, received 0.3% adenine diet for 10 weeks and normal chow for additional 8 weeks. Urine and blood samples were collected to evaluate the induction of CKD. Heart function was assessed by echocardiography. The sensitivity to myocardial IRI was assessed ex vivo. Inflammation profile of rats with CKD was assessed via RNA sequencing, ELISA and tissue histology. Results Induction of CKD was confirmed by a significant increase in serum creatine and urinary albumin to creatine ratio. Histology revealed extensive glomerular and tubular damage. Diastolic dysfunction, measured by the reduction of E/A ratio, was apparent in rats with CKD from 16 weeks. Hearts from rats with CKD had significantly larger infarcts compared to control hearts, indicating impaired resistance to IRI. The CKD rats also had higher levels of inflammatory cytokines including MPO, IL-6 and IL-33; and RNA sequencing revealed increase in inflammatory signalling pathways. Conclusion We have established a modified model of adenine-induced CKD model, which leads to cardiovascular dysfunction that is maintained up to two months following return to normal diet. Conflict of Interest None