Development of a pediatric pig model of extracorporeal cardiopulmonary resuscitation (ECPR) induced acute kidney injury.

Acute kidney injury (AKI) is a common and severe morbidity following extracorporeal cardiopulmonary resuscitation (ECPR), particularly in children, where AKI is associated with a 4-fold increased risk of death. Research into the mechanisms and treatment of ECPR-induced AKI is hampered by the lack of relevant translational models. In this study, we developed a pediatric swine model of ECPR-induced AKI and defined the histological and transcriptomic changes seen in the kidney following ECPR. Four infant swine underwent hyperkalemic cardiac arrest (5, 10, 15, or 20 min) followed by 4 hours of ECMO. Mechanically ventilated animals (n=9) were used for comparison. ECPR animals demonstrated progressive histologic, biomarker, and physiologic kidney injury with increasing cardiac arrest time. All ECPR-exposed animals demonstrated a distinct transcriptomic response compared to controls, with 1,433 differentially expressed genes covering a range of biologic systems including oxidative stress, renal angiogenesis and solute channel formation, protein folding/misfolding, and ribosome biogenesis. This study demonstrates the ability to model ECPR-induced kidney injury in a titratable fashion and to serve as a platform for mechanistic and therapeutic studies for this important morbidity.