Cardiac effects of renal ischemia.

Abstract

Mortality in acute kidney injury (AKI) remains very high, yet the cause of death is often failure of extrarenal organs. We and others have demonstrated remote organ dysfunction after renal ischemia. The term "cardiorenal syndrome" was first applied to the "cross talk" between the organs by the National Heart, Lung, and Blood Institute of the National Institutes of Health, and the clinical importance is being increasingly appreciated. Nevertheless, more information is needed to effectively address the consequences of renal injury on the heart. Since AKI often occurs in patients with comorbidities, we investigated the effect of renal ischemia in the setting of existing cardiac failure. We hypothesized that the cardiac effects of renal ischemia would be significantly amplified in experimental cardiomyopathy. Male Sprague-Dawley rats with preexisting cardiac and renal injury due to low-dose doxorubicin were subjected to bilateral renal artery occlusion. Cardiac structure and function were examined 2 days after reperfusion. Loss of functional myocardial tissue with decreases in left ventricular pressure, increases in apoptotic cell death, inflammation, and collagen, and greater disruption in ultrastructure with mitochondrial fragmentation were seen in the doxorubicin/ischemia group compared with animals in the groups treated with doxorubicin alone or following ischemia alone. Systemic inflammation and cardiac abnormalities persisted for at least 21 wk. These results suggest that preexisting comorbidities can result in much more severe distant organ effects of acute renal injury. The results of this study are relevant to human AKI.NEW & NOTEWORTHY Acute kidney injury is common, expensive, and deadly, yet morbidity and mortality are often secondary to remote organ dysfunction. We hypothesized that the effects of renal ischemia would be amplified in the setting of comorbidities. Sustained systemic inflammation and loss of functional myocardium with significantly decreased systolic and diastolic function, apoptotic cell death, and increased collagen and inflammatory cells were found in the heart after renal ischemia in the doxorubicin cardiomyopathy model (vs. renal ischemia alone). Understanding the remote effects of renal ischemia has the potential to improve outcomes in acute kidney injury.