Development of a pediatric pig model of extracorporeal cardiopulmonary resuscitation-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 fourfold 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 for 5, 10, 15 or 20 min, followed by 4 h of extracorporeal membrane oxygenation. 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 1433 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, serving as a platform for mechanistic and therapeutic studies for this important morbidity.