The effect of adenosine agonist, Regadenoson, on acute kidney injury in a pig model of extracorporeal cardiopulmonary resuscitation

Extracorporeal Cardiopulmonary Resuscitation (ECPR) is a life-saving therapy for patients with cardiac arrest, particularly infants with congenital heart disease. However, there are many potential complications of ECPR including acute kidney injury (AKI). Currently, there are no clinical therapies to mitigate AKI. We hypothesized that Regadenoson, an A2A adenosine receptor agonist, would reduce the degree of AKI in a pig model of ECPR. Cardiac arrest was stimulated in mature domestic swine, followed by 6 hours of extracorporeal membrane oxygenation (ECMO). Each pig received either low (1.44 mcg/kg/h) or high (14.4 mcg/kg/h) dose Regadenoson or a saline control. Blood and urine were collected at 0, 3, 6, 12, and 24 hours when the animals were euthanized. Kidney samples were prepared for histological assessment and reviewed blindly by a renal pathologist for inflammation, thrombi, and interstitial infiltration. Renal dysfunction was assessed through serum creatinine and blood urea nitrogen (BUN) levels. In the pilot study, there is not a difference in the serum creatinine levels over 24 hours in pigs exposed to either low or high dose Regadenoson compared to the control group. Creatinine, however, is a poor and late marker of renal dysfunction and we will focus efforts on histological evaluation of the kidneys. Our goal is to identify an efficient therapy reducing the degree of AKI resulting from ECPR. This may lead to future therapies that can lessen the number of children who develop chronic kidney disease (CKD) as a result of AKI sustained from ECPR.