Rats with adenine-induced chronic kidney disease had significantly larger myocardial infarcts after ischemia-reperfusion injury compared to controls (38.8% vs. 26.3%, P < 0.003), accompanied by cardiac capillary rarefaction and systemic inflammation.
A modified adenine-induced CKD rat model shows that CKD induces persistent diastolic dysfunction, increased sensitivity to ischemia-reperfusion injury, and cardiac capillary rarefaction even after adenine withdrawal.
Absolute Event Rate: 38.8% vs 26.3%
p-value: p=<0.003
Myocardial ischemia-reperfusion (IR) injury is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD). The most frequently used and representative experimental model is the rat dietary adenine-induced CKD, which leads to CKD-associated CVD. However, the continued intake of adenine is a potential confounding factor. This study investigated cardiovascular dysfunction following brief adenine exposure, CKD development and return to a normal diet. Male Wistar rats received a 0.3% adenine diet for 10 weeks and normal chow for an additional 8 weeks. Kidney function was assessed by urinalysis and histology. Heart function was assessed by echocardiography. Sensitivity to myocardial IR injury was assessed using the isolated perfused rat heart (Langendorff) model. The inflammation profile of rats with CKD was assessed via cytokine ELISA, tissue histology and RNA sequencing. Induction of CKD was confirmed by a significant increase in plasma creatinine and albuminuria. Histology revealed extensive glomerular and tubular damage. Diastolic dysfunction, measured by the reduction of the E/A ratio, was apparent in rats with CKD even following a normal diet. Hearts from rats with CKD had significantly larger infarcts after IR injury. The CKD rats also had statistically higher levels of markers of inflammation including myeloperoxidase, KIM-1 and interleukin-33. RNA sequencing revealed several changes including an increase in inflammatory signaling pathways. In addition, we noted that CKD induced significant cardiac capillary rarefaction. We have established a modified model of adenine-induced CKD, which leads to cardiovascular dysfunction in the absence of adenine. Our observations of capillary rarefaction and inflammation suggest that these may contribute to detrimental cardiovascular outcomes.
Kalkhoran et al. (Wed,) conducted a other in Chronic Kidney Disease and Cardiovascular Dysfunction (n=32). Adenine-enriched diet vs. Normal chow was evaluated on Myocardial infarct size following ischemia-reperfusion injury (IS/AAR%) (p=<0.003). Rats with adenine-induced chronic kidney disease had significantly larger myocardial infarcts after ischemia-reperfusion injury compared to controls (38.8% vs. 26.3%, P < 0.003), accompanied by cardiac capillary rarefaction and systemic inflammation.
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